11-17439352-T-C

Position:

• chr11-17439352-T-C

Variant summary

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

The NM_000352.6(ABCC8):​c.1630+3368A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,836 control chromosomes in the GnomAD database, including 17,202 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 0.46 (17202 hom., cov: 31)
• Consequence: ABCC8 NM_000352.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC8	NM_000352.6	c.1630+3368A>G		intron_variant		ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC8	ENST00000389817.8	c.1630+3368A>G		intron_variant		1	NM_000352.6	P4

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69340 AN: 151718 Hom.: 17173 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.418

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.449

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

GnomAD4 genome AF: 0.457 AC: 69419 AN: 151836 Hom.: 17202 Cov.: 31 AF XY: 0.450 AC XY: 33393 AN XY: 74216

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.418

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.445

Alfa AF: 0.426 Hom.: 5132

Bravo AF: 0.477

Asia WGS AF: 0.323 AC: 1124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.45

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: rs2237981; hg19: chr11-17460899;