rs1799854

Variant names:

• chr11-17427157-G-A
• rs1799854
• NM_000352.6:c.2117-3C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17427157-G-A
• chr11-17427157-G-C
• chr11-17427157-G-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_000352.6(ABCC8):​c.2117-3C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,608,952 control chromosomes in the GnomAD database, including 148,402 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (12005 hom., cov: 31)
  • Exomes 𝑓: 0.43 (136397 hom.)
• Consequence: ABCC8 NM_000352.6 splice_region, intron
• Scores: Splicing: ADA: 0.1129
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:16 O:1
• Conservation: PhyloP100: 2.82

Genes affected

ABCC8 (HGNC:59): (ATP binding cassette subfamily C member 8) The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions as a modulator of ATP-sensitive potassium channels and insulin release. Mutations in the ABCC8 gene and deficiencies in the encoded protein have been observed in patients with hyperinsulinemic hypoglycemia of infancy, an autosomal recessive disorder of unregulated and high insulin secretion. Mutations have also been associated with non-insulin-dependent diabetes mellitus type II, an autosomal dominant disease of defective insulin secretion. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2020]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 11-17427157-G-A is Benign according to our data. Variant chr11-17427157-G-A is described in ClinVar as [Benign]. Clinvar id is 157688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC8	NM_000352.6	c.2117-3C>T		splice_region_variant, intron_variant	Intron 15 of 38	ENST00000389817.8	NP_000343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC8	ENST00000389817.8	c.2117-3C>T		splice_region_variant, intron_variant	Intron 15 of 38	1	NM_000352.6	ENSP00000374467.4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56513 AN: 151924 Hom.: 11999 Cov.: 31

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.344

Gnomad FIN AF: 0.436

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.406

GnomAD3 exomes AF: 0.440 AC: 108736 AN: 246958 Hom.: 25627 AF XY: 0.433 AC XY: 57896 AN XY: 133576

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.459

Gnomad EAS exome AF: 0.596

Gnomad SAS exome AF: 0.325

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.428

GnomAD4 exome AF: 0.427 AC: 622485 AN: 1456910 Hom.: 136397 Cov.: 36 AF XY: 0.425 AC XY: 308010 AN XY: 724320

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.597

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.540

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.433

Gnomad4 NFE exome AF: 0.431

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.372 AC: 56535 AN: 152042 Hom.: 12005 Cov.: 31 AF XY: 0.374 AC XY: 27762 AN XY: 74284

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.499

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.436

Gnomad4 NFE AF: 0.438

Gnomad4 OTH AF: 0.404

Alfa AF: 0.437 Hom.: 19049

Bravo AF: 0.373

Asia WGS AF: 0.404 AC: 1409 AN: 3478

EpiCase AF: 0.441

EpiControl AF: 0.442

ClinVar

Significance: Benign

Submissions summary: Benign:16 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Apr 30, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 26740944, 29469970, 16429405, 15807877, 8635661, 25525159, 22533711, 10333056, 10857971, 20079163) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:3

-

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 19, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diabetes mellitus, transient neonatal, 2 Benign:2

Jul 01, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Hyperinsulinemic hypoglycemia, familial, 1 Benign:2

Jul 01, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Hereditary hyperinsulinism Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Leucine-induced hypoglycemia Benign:1

Jul 01, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Type 2 diabetes mellitus;C0271714:Leucine-induced hypoglycemia;C1835887:Diabetes mellitus, transient neonatal, 2;C2931832:Hyperinsulinemic hypoglycemia, familial, 1;C5394303:Diabetes mellitus, permanent neonatal 3 Benign:1

May 04, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diabetes mellitus, permanent neonatal 3 Benign:1

Jul 01, 2021

Pars Genome Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Permanent neonatal diabetes mellitus Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Type 2 diabetes mellitus Other:1

-

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance: association

Review Status: no assertion criteria provided

Collection Method: research

Mutations in this gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation have a better response to sulfonylureas. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	15
DANN	Benign	0.94

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.11
dbscSNV1_RF	Benign	0.12
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1799854; hg19: chr11-17448704;