rs3842748

Positions:

• chr11-2160165-C-G
• chr11-2160165-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000207.3(INS):​c.188-168G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,124 control chromosomes in the GnomAD database, including 37,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (37104 hom., cov: 33)
• Consequence: INS NM_000207.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

Genes affected

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]

INS-IGF2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 11-2160165-C-G is Benign according to our data. Variant chr11-2160165-C-G is described in ClinVar as [Benign]. Clinvar id is 1239524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
INS	NM_000207.3	c.188-168G>C		intron_variant		ENST00000381330.5	NP_000198.1
INS-IGF2	NR_003512.4	n.246+620G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INS	ENST00000381330.5	c.188-168G>C		intron_variant		1	NM_000207.3	ENSP00000370731	P1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100999 AN: 152006 Hom.: 37091 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.770

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.957

Gnomad SAS AF: 0.865

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.860

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.664 AC: 101041 AN: 152124 Hom.: 37104 Cov.: 33 AF XY: 0.677 AC XY: 50336 AN XY: 74358

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.770

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.957

Gnomad4 SAS AF: 0.866

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.734

Alfa AF: 0.709 Hom.: 4842

Bravo AF: 0.643

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	-0.78
CADD	Benign	5.3
DANN	Benign	0.85

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: rs3842748; hg19: chr11-2181395;