Variant chr11-17444498-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.593

Variant links:

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]

ABCC8 links:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.1333-1186T>G		intron_variant		ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ABCC8	ENST00000389817.8 linkuse as main transcript	c.1333-1186T>G		intron_variant		1	NM_000352.6	P4	Q09428-1

Frequencies

GnomAD3 genomes

AF:

0.406

AC:

61593

AN:

151748

Hom.:

13513

Cov.:

show subpopulations

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:

AN:

200

Hom.:

AF XY:

0.361

AC XY:

AN XY:

158

show subpopulations

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.:

AF XY:

0.397

AC XY:

29482

AN XY:

74226

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over