rs3842738

Positions:

• chr11-2161265-C-G
• chr11-2161265-C-T

Variant summary

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

The variant allele was found at a frequency of 0.942 in 396,288 control chromosomes in the GnomAD database, including 179,581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.88 (61547 hom., cov: 35)
  • Exomes 𝑓: 0.98 (118034 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61

Genes affected

(HGNC:):

INS (HGNC:6081): (insulin) This gene encodes insulin, a peptide hormone that plays a vital role in the regulation of carbohydrate and lipid metabolism. After removal of the precursor signal peptide, proinsulin is post-translationally cleaved into three peptides: the B chain and A chain peptides, which are covalently linked via two disulfide bonds to form insulin, and C-peptide. Binding of insulin to the insulin receptor (INSR) stimulates glucose uptake. A multitude of mutant alleles with phenotypic effects have been identified, including insulin-dependent diabetes mellitus, permanent neonatal diabetes diabetes mellitus, maturity-onset diabetes of the young type 10 and hyperproinsulinemia. There is a read-through gene, INS-IGF2, which overlaps with this gene at the 5' region and with the IGF2 gene at the 3' region. [provided by RefSeq, May 2020]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-2161265-C-G is Benign according to our data. Variant chr11-2161265-C-G is described in ClinVar as [Benign]. Clinvar id is 1291923.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.2161265C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INS	ENST00000250971.7	c.-141G>C		upstream_gene_variant		1		ENSP00000250971.3

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134097 AN: 152054 Hom.: 61515 Cov.: 35

Gnomad AFR AF: 0.594

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.982

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.913

GnomAD4 exome AF: 0.980 AC: 239303 AN: 244116 Hom.: 118034 Cov.: 3 AF XY: 0.983 AC XY: 122299 AN XY: 124464

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.968

Gnomad4 ASJ exome AF: 0.985

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.882 AC: 134181 AN: 152172 Hom.: 61547 Cov.: 35 AF XY: 0.887 AC XY: 66019 AN XY: 74406

Gnomad4 AFR AF: 0.594

Gnomad4 AMR AF: 0.951

Gnomad4 ASJ AF: 0.982

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.914

Alfa AF: 0.931 Hom.: 7943

Bravo AF: 0.864

Asia WGS AF: 0.977 AC: 3399 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	Mar 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.60
DANN	Benign	0.38

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3842738; hg19: chr11-2182495;