rs886292

Positions:

• chr11-17444498-A-C
• chr11-17444498-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000352.6(ABCC8):​c.1333-1186T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 152,066 control chromosomes in the GnomAD database, including 13,548 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13529 hom., cov: 31)
  • Exomes 𝑓: 0.39 (19 hom.)
• Consequence: ABCC8 NM_000352.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.593

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-17444498-A-C is Benign according to our data. Variant chr11-17444498-A-C is described in ClinVar as [Benign]. Clinvar id is 1246345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.572 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ABCC8	NM_000352.6	c.1333-1186T>G		intron_variant		ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC8	ENST00000389817.8	c.1333-1186T>G		intron_variant		1	NM_000352.6	P4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61593 AN: 151748 Hom.: 13513 Cov.: 31

Gnomad AFR AF: 0.578

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.541

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.385 AC: 77 AN: 200 Hom.: 19 AF XY: 0.361 AC XY: 57 AN XY: 158

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.667

Gnomad4 NFE exome AF: 0.409

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.406 AC: 61653 AN: 151866 Hom.: 13529 Cov.: 31 AF XY: 0.397 AC XY: 29482 AN XY: 74226

Gnomad4 AFR AF: 0.578

Gnomad4 AMR AF: 0.395

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.284

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.418

Alfa AF: 0.209 Hom.: 384

Bravo AF: 0.428

Asia WGS AF: 0.269 AC: 937 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs886292; hg19: chr11-17466045; COSMIC: COSV56858385; COSMIC: COSV56858385;