rs1801261

Variant names:

• chr11-17415318-G-A
• rs1801261
• NM_000352.6:c.2277C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-17415318-G-A
• chr11-17415318-G-C
• chr11-17415318-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000352.6(ABCC8):​c.2277C>T​(p.Thr759Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0422 in 1,610,186 control chromosomes in the GnomAD database, including 1,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (94 hom., cov: 33)
  • Exomes 𝑓: 0.044 (1661 hom.)
• Consequence: ABCC8 NM_000352.6 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -0.480

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-17415318-G-A is Benign according to our data. Variant chr11-17415318-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 157689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17415318-G-A is described in Lovd as [Benign]. Variant chr11-17415318-G-A is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-0.48 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABCC8	NM_000352.6	c.2277C>T	p.Thr759Thr	synonymous_variant	Exon 18 of 39	ENST00000389817.8	NP_000343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABCC8	ENST00000389817.8	c.2277C>T	p.Thr759Thr	synonymous_variant	Exon 18 of 39	1	NM_000352.6	ENSP00000374467.4

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4273 AN: 152128 Hom.: 94 Cov.: 33

Gnomad AFR AF: 0.00881

Gnomad AMI AF: 0.0429

Gnomad AMR AF: 0.0217

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.0277

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0461

Gnomad OTH AF: 0.0182

GnomAD3 exomes AF: 0.0272 AC: 6624 AN: 243136 Hom.: 142 AF XY: 0.0273 AC XY: 3577 AN XY: 130962

Gnomad AFR exome AF: 0.00754

Gnomad AMR exome AF: 0.0132

Gnomad ASJ exome AF: 0.00995

Gnomad EAS exome AF: 0.000166

Gnomad SAS exome AF: 0.00885

Gnomad FIN exome AF: 0.0297

Gnomad NFE exome AF: 0.0445

Gnomad OTH exome AF: 0.0301

GnomAD4 exome AF: 0.0437 AC: 63700 AN: 1457940 Hom.: 1661 Cov.: 31 AF XY: 0.0423 AC XY: 30687 AN XY: 724626

Gnomad4 AFR exome AF: 0.00699

Gnomad4 AMR exome AF: 0.0127

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00952

Gnomad4 FIN exome AF: 0.0318

Gnomad4 NFE exome AF: 0.0523

Gnomad4 OTH exome AF: 0.0343

GnomAD4 genome AF: 0.0281 AC: 4271 AN: 152246 Hom.: 94 Cov.: 33 AF XY: 0.0267 AC XY: 1990 AN XY: 74440

Gnomad4 AFR AF: 0.00878

Gnomad4 AMR AF: 0.0216

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.0277

Gnomad4 NFE AF: 0.0461

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0422 Hom.: 276

Bravo AF: 0.0267

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 14, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Sep 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24768178, 22902787, 9075812, 25955821, 24959012, 22704848, 18758683, 18599530, 15842514, 15111507, 11246895, 31118371, 11289470) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 27, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Inborn genetic diseases Benign:1

May 24, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Hereditary hyperinsulinism Benign:1

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diabetes mellitus, transient neonatal, 2 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Hyperinsulinemic hypoglycemia, familial, 1 Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Permanent neonatal diabetes mellitus Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.20
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs1801261; hg19: chr11-17436865;