rs2074311

chr11-17400313-A-Gchr11-17400313-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000352.6(ABCC8):c.3651-1872T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,016 control chromosomes in the GnomAD database, including 32,874 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32874 hom., cov: 31)
• Consequence: ABCC8 NM_000352.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.563

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC8	NM_000352.6	c.3651-1872T>C		intron_variant		ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC8	ENST00000389817.8	c.3651-1872T>C		intron_variant		1	NM_000352.6	P4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98078 AN: 151898 Hom.: 32820 Cov.: 31

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.609

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 98193 AN: 152016 Hom.: 32874 Cov.: 31 AF XY: 0.642 AC XY: 47678 AN XY: 74274

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.616

Gnomad4 ASJ AF: 0.472

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.558

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.574

Gnomad4 OTH AF: 0.610

Alfa AF: 0.582 Hom.: 33937

Bravo AF: 0.660

Asia WGS AF: 0.632 AC: 2199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	7.4
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs2074311; hg19: chr11-17421860;