11-17419233-G-C

Position:

• chr11-17419233-G-C

Variant summary

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

The ENST00000389817.8(ABCC8):​c.2223-2271C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 152,136 control chromosomes in the GnomAD database, including 14,055 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 0.40 (14055 hom., cov: 33)
• Consequence: ABCC8 ENST00000389817.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABCC8	NM_000352.6	c.2223-2271C>G		intron_variant		ENST00000389817.8	NP_000343.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABCC8	ENST00000389817.8	c.2223-2271C>G		intron_variant		1	NM_000352.6	ENSP00000374467	P4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60594 AN: 152018 Hom.: 14038 Cov.: 33

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.399 AC: 60665 AN: 152136 Hom.: 14055 Cov.: 33 AF XY: 0.402 AC XY: 29878 AN XY: 74384

Gnomad4 AFR AF: 0.649

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.368

Alfa AF: 0.221 Hom.: 571

Bravo AF: 0.403

Asia WGS AF: 0.363 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.7
DANN	Benign	0.66

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: rs916828; hg19: chr11-17440780;