rs3741211

Variant names:

• chr11-2147880-A-G
• rs3741211
• ENST00000397270.1:c.408-73T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-2147880-A-G
• chr11-2147880-A-T

Variant summary

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

The NM_001042376.3(INS-IGF2):​c.408-73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 1,112,480 control chromosomes in the GnomAD database, including 79,314 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 0.36 (9993 hom., cov: 30)
  • Exomes 𝑓: 0.38 (69321 hom.)
• Consequence: INS-IGF2 NM_001042376.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• Publications: 26 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 (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-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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042376.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INS-IGF2	NM_001042376.3		c.408-73T>C		intron	N/A	NP_001035835.1	F8WCM5-1
	IGF2	NM_001007139.6		c.-248-73T>C		intron	N/A	NP_001007140.2	P01344-1
	IGF2-AS	NR_028043.2		n.1282A>G		non_coding_transcript_exon	Exon 3 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INS-IGF2	ENST00000397270.1	TSL:1	c.408-73T>C		intron	N/A	ENSP00000380440.1	F8WCM5-1
	ENSG00000284779	ENST00000643349.2		c.255-73T>C		intron	N/A	ENSP00000495715.1	A0A2R8Y747
	IGF2	ENST00000481781.3	TSL:5	c.-248-73T>C		intron	N/A	ENSP00000511998.1	P01344-1

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54492 AN: 151512 Hom.: 9989 Cov.: 30

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.331

GnomAD4 exome AF: 0.378 AC: 363219 AN: 960846 Hom.: 69321 Cov.: 14 AF XY: 0.377 AC XY: 172250 AN XY: 456882

African (AFR) AF: 0.394 AC: 8301 AN: 21060

American (AMR) AF: 0.278 AC: 2303 AN: 8276

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 4445 AN: 13670

East Asian (EAS) AF: 0.294 AC: 7643 AN: 25960

South Asian (SAS) AF: 0.268 AC: 4639 AN: 17328

European-Finnish (FIN) AF: 0.346 AC: 7585 AN: 21922

Middle Eastern (MID) AF: 0.277 AC: 789 AN: 2848

European-Non Finnish (NFE) AF: 0.387 AC: 313292 AN: 809914

Other (OTH) AF: 0.357 AC: 14222 AN: 39868

GnomAD4 genome AF: 0.360 AC: 54521 AN: 151634 Hom.: 9993 Cov.: 30 AF XY: 0.354 AC XY: 26221 AN XY: 74128

African (AFR) AF: 0.395 AC: 16319 AN: 41332

American (AMR) AF: 0.282 AC: 4309 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1157 AN: 3470

East Asian (EAS) AF: 0.282 AC: 1441 AN: 5102

South Asian (SAS) AF: 0.267 AC: 1279 AN: 4798

European-Finnish (FIN) AF: 0.340 AC: 3586 AN: 10538

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25239 AN: 67838

Other (OTH) AF: 0.332 AC: 697 AN: 2100

Alfa AF: 0.365 Hom.: 17614

Bravo AF: 0.356

Asia WGS AF: 0.313 AC: 1091 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.63
PhyloP100		0.10
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: rs3741211; hg19: chr11-2169110;