rs3741208

Variant names:

• chr11-2148544-A-G
• rs3741208
• ENST00000397270.1:c.407+582T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2148544-A-G
• chr11-2148544-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397270.1(INS-IGF2):​c.407+582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 153,680 control chromosomes in the GnomAD database, including 30,765 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (30490 hom., cov: 32)
  • Exomes 𝑓: 0.55 (275 hom.)
• Consequence: INS-IGF2 ENST00000397270.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 44 publications found

Genes affected

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]

ENSG00000284779 (HGNC:):

IGF2-AS (HGNC:14062): (IGF2 antisense RNA) This gene is expressed in antisense to the insulin-like growth factor 2 (IGF2) gene and is imprinted and paternally expressed. It is thought to be non-coding because the putative protein is not conserved and translation is predicted to trigger nonsense mediated decay (NMD). Transcripts from this gene are produced in tumors and may function to suppress cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2015]

IGF2 (HGNC:5466): (insulin like growth factor 2) This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

IGF2 Gene-Disease associations (from GenCC):

• Silver-Russell syndrome 3

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Illumina

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397270.1. 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
	IGF2-AS	NR_028043.2		n.1946A>G		non_coding_transcript_exon	Exon 3 of 3
	IGF2-AS	NR_133657.1		n.1835A>G		non_coding_transcript_exon	Exon 3 of 3
	INS-IGF2	NM_001042376.3		c.407+582T>C		intron	N/A	NP_001035835.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INS-IGF2	ENST00000397270.1	TSL:1	c.407+582T>C		intron	N/A	ENSP00000380440.1
	ENSG00000284779	ENST00000643349.2		c.254+582T>C		intron	N/A	ENSP00000495715.1
	IGF2-AS	ENST00000381361.4	TSL:2	n.1941A>G		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95745 AN: 151810 Hom.: 30472 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.549 AC: 962 AN: 1752 Hom.: 275 Cov.: 0 AF XY: 0.560 AC XY: 493 AN XY: 880

African (AFR) AF: 0.591 AC: 26 AN: 44

American (AMR) AF: 0.414 AC: 24 AN: 58

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 28 AN: 52

East Asian (EAS) AF: 0.745 AC: 82 AN: 110

South Asian (SAS) AF: 0.600 AC: 6 AN: 10

European-Finnish (FIN) AF: 0.372 AC: 35 AN: 94

Middle Eastern (MID) AF: 0.667 AC: 4 AN: 6

European-Non Finnish (NFE) AF: 0.552 AC: 700 AN: 1268

Other (OTH) AF: 0.518 AC: 57 AN: 110

GnomAD4 genome AF: 0.631 AC: 95795 AN: 151928 Hom.: 30490 Cov.: 32 AF XY: 0.629 AC XY: 46702 AN XY: 74266

African (AFR) AF: 0.642 AC: 26591 AN: 41408

American (AMR) AF: 0.512 AC: 7824 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2191 AN: 3470

East Asian (EAS) AF: 0.810 AC: 4179 AN: 5162

South Asian (SAS) AF: 0.731 AC: 3528 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6183 AN: 10540

Middle Eastern (MID) AF: 0.655 AC: 190 AN: 290

European-Non Finnish (NFE) AF: 0.637 AC: 43287 AN: 67944

Other (OTH) AF: 0.631 AC: 1331 AN: 2108

Alfa AF: 0.630 Hom.: 54314

Bravo AF: 0.625

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3741208; hg19: chr11-2169774;