rs1799859

Positions:

chr11-17397732-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000352.6(ABCC8):c.3819G>A(p.Arg1273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,552 control chromosomes in the GnomAD database, including 76,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 14758 hom., cov: 33)

Exomes 𝑓: 0.28 ( 62188 hom. )

Consequence

ABCC8
NM_000352.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 0.348

Variant links:

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]

ABCC8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 11-17397732-C-T is Benign according to our data. Variant chr11-17397732-C-T is described in ClinVar as [Benign]. Clinvar id is 157698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-17397732-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.348 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC8	NM_000352.6 linkuse as main transcript	c.3819G>A	p.Arg1273=	synonymous_variant	31/39	ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC8	ENST00000389817.8 linkuse as main transcript	c.3819G>A	p.Arg1273=	synonymous_variant	31/39	1	NM_000352.6	P4	Q09428-1

Frequencies

GnomAD3 genomes

AF:

0.387

AC:

58825

AN:

152050

Hom.:

14720

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.186

Gnomad AMR

AF:

0.399

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0878

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.291

AC:

72932

AN:

250196

Hom.:

13041

AF XY:

0.283

AC XY:

38357

AN XY:

135316

show subpopulations

Gnomad AFR exome

AF:

0.714

Gnomad AMR exome

AF:

0.391

Gnomad ASJ exome

AF:

0.252

Gnomad EAS exome

AF:

0.0832

Gnomad SAS exome

AF:

0.292

Gnomad FIN exome

AF:

0.155

Gnomad NFE exome

AF:

0.264

Gnomad OTH exome

AF:

0.280

GnomAD4 exome

AF:

0.278

AC:

406876

AN:

1461384

Hom.:

62188

Cov.:

AF XY:

0.277

AC XY:

201664

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.726

Gnomad4 AMR exome

AF:

0.391

Gnomad4 ASJ exome

AF:

0.255

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.298

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.290

GnomAD4 genome

AF:

0.387

AC:

58918

AN:

152168

Hom.:

14758

Cov.:

AF XY:

0.379

AC XY:

28230

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.400

Gnomad4 ASJ

AF:

0.251

Gnomad4 EAS

AF:

0.0882

Gnomad4 SAS

AF:

0.295

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.361

Alfa

AF:

0.289

Hom.:

15637

Bravo

AF:

0.417

Asia WGS

AF:

0.230

AC:

805

AN:

3478

EpiCase

AF:

0.270

EpiControl

AF:

0.277

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 19, 2014	- -

Hyperinsulinemic hypoglycemia, familial, 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Apr 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	This variant is associated with the following publications: (PMID: 9799081, 22533711, 10857971, 18758683) -

Type 2 diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. rs1799859 of ABCC8 gene is associated with Hb1Ac levels and its genotype might impact the Sulfonylurea treatment reponse. -

Hereditary hyperinsulinism

Benign:1

Benign, no assertion criteria provided

clinical testing

Natera, Inc.

Sep 16, 2020

- -

Leucine-induced hypoglycemia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

Hyperinsulinism, Dominant/Recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Diabetes mellitus, transient neonatal, 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

Diabetes mellitus, permanent neonatal 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Pars Genome Lab

Jul 01, 2021

- -

Permanent neonatal diabetes mellitus

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Transient Neonatal Diabetes, Dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

9.9

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over