rs3842748

Variant names:

• chr11-2160165-C-G
• rs3842748
• NM_000207.3:c.188-168G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 31 publications found

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:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

ENSG00000295384 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000207.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INS	NM_000207.3	MANE Select	c.188-168G>C		intron	N/A	NP_000198.1
	INS-IGF2	NM_001042376.3		c.187+620G>C		intron	N/A	NP_001035835.1
	INS	NM_001185097.2		c.188-168G>C		intron	N/A	NP_001172026.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INS	ENST00000381330.5	TSL:1 MANE Select	c.188-168G>C		intron	N/A	ENSP00000370731.5
	INS-IGF2	ENST00000397270.1	TSL:1	c.187+620G>C		intron	N/A	ENSP00000380440.1
	INS	ENST00000250971.7	TSL:1	c.188-168G>C		intron	N/A	ENSP00000250971.3

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

African (AFR) AF: 0.318 AC: 13209 AN: 41504

American (AMR) AF: 0.770 AC: 11776 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3470

East Asian (EAS) AF: 0.957 AC: 4924 AN: 5146

South Asian (SAS) AF: 0.866 AC: 4177 AN: 4824

European-Finnish (FIN) AF: 0.844 AC: 8964 AN: 10616

Middle Eastern (MID) AF: 0.863 AC: 252 AN: 292

European-Non Finnish (NFE) AF: 0.779 AC: 52907 AN: 67956

Other (OTH) AF: 0.734 AC: 1551 AN: 2112

Alfa AF: 0.709 Hom.: 4842

Bravo AF: 0.643

Asia WGS AF: 0.867 AC: 3016 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3842748; hg19: chr11-2181395;