11-17476848-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The ENST00000662030.1(ENSG00000287898):n.137+117C>T variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00566 in 1,260,076 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0059 (18 hom.)
• Consequence: ENST00000662030.1 intron, non_coding_transcript
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.905

Genes affected

(HGNC:):

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-17476848-C-T is Benign according to our data. Variant chr11-17476848-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 303791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902641	XR_007062609.1	n.81+117C>T		intron_variant, non_coding_transcript_variant
ABCC8	NM_000352.6			upstream_gene_variant		ENST00000389817.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000662030.1	n.137+117C>T		intron_variant, non_coding_transcript_variant
ABCC8	ENST00000389817.8			upstream_gene_variant		1	NM_000352.6	P4

Frequencies

GnomAD3 genomes AF: 0.00424 AC: 643 AN: 151772 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00893

Gnomad ASJ AF: 0.00923

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000573

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00596

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.0110 AC: 110 AN: 9982 Hom.: 0 AF XY: 0.0108 AC XY: 57 AN XY: 5292

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0920

Gnomad ASJ exome AF: 0.0833

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0307

Gnomad FIN exome AF: 0.000380

Gnomad NFE exome AF: 0.0181

Gnomad OTH exome AF: 0.0373

GnomAD4 exome AF: 0.00585 AC: 6483 AN: 1108196 Hom.: 18 Cov.: 30 AF XY: 0.00580 AC XY: 3070 AN XY: 529068

Gnomad4 AFR exome AF: 0.00113

Gnomad4 AMR exome AF: 0.0110

Gnomad4 ASJ exome AF: 0.00859

Gnomad4 EAS exome AF: 0.0000398

Gnomad4 SAS exome AF: 0.00370

Gnomad4 FIN exome AF: 0.000876

Gnomad4 NFE exome AF: 0.00624

Gnomad4 OTH exome AF: 0.00653

GnomAD4 genome AF: 0.00423 AC: 643 AN: 151880 Hom.: 6 Cov.: 33 AF XY: 0.00385 AC XY: 286 AN XY: 74244

Gnomad4 AFR AF: 0.00108

Gnomad4 AMR AF: 0.00892

Gnomad4 ASJ AF: 0.00923

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.000573

Gnomad4 NFE AF: 0.00597

Gnomad4 OTH AF: 0.00711

Alfa AF: 0.00475 Hom.: 0

Bravo AF: 0.00499

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jul 20, 2017

- -

Hyperinsulinism, Dominant/Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Maturity onset diabetes mellitus in young Benign:1

Benign, criteria provided, single submitter

research

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

-

Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a response to sulfonylureas. However, no association is found between this particular variant (rs541244107) of ABCC8 gene and MODY yet. -

Permanent neonatal diabetes mellitus Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Transient Neonatal Diabetes, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	14
Dann	Benign	0.97

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs541244107; hg19: chr11-17498395;