rs11024298

Positions:

• chr11-17470284-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000352.6(ABCC8):​c.291-62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,610,324 control chromosomes in the GnomAD database, including 2,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (1248 hom., cov: 32)
  • Exomes 𝑓: 0.011 (1203 hom.)
• Consequence: ABCC8 NM_000352.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.317

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-17470284-C-A is Benign according to our data. Variant chr11-17470284-C-A is described in ClinVar as [Benign]. Clinvar id is 1251559.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC8	NM_000352.6	c.291-62G>T		intron_variant		ENST00000389817.8	NP_000343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC8	ENST00000389817.8	c.291-62G>T		intron_variant		1	NM_000352.6	ENSP00000374467	P4

Frequencies

GnomAD3 genomes AF: 0.0738 AC: 11227 AN: 152106 Hom.: 1240 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0389

Gnomad ASJ AF: 0.0573

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00621

Gnomad FIN AF: 0.000753

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.00366

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0111 AC: 16232 AN: 1458100 Hom.: 1203 Cov.: 32 AF XY: 0.0105 AC XY: 7580 AN XY: 725018

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.0191

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00915

Gnomad4 FIN exome AF: 0.000664

Gnomad4 NFE exome AF: 0.00265

Gnomad4 OTH exome AF: 0.0255

GnomAD4 genome AF: 0.0740 AC: 11262 AN: 152224 Hom.: 1248 Cov.: 32 AF XY: 0.0709 AC XY: 5278 AN XY: 74432

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0573

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.000753

Gnomad4 NFE AF: 0.00366

Gnomad4 OTH AF: 0.0559

Alfa AF: 0.0205 Hom.: 219

Bravo AF: 0.0854

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.2
DANN	Benign	0.63

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: rs11024298; hg19: chr11-17491831;