rs3213232

Variant names:

• chr11-2133734-G-A
• rs3213232
• NM_000612.6:c.158-69C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-2133734-G-A
• chr11-2133734-G-C
• chr11-2133734-G-T

Variant summary

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

The NM_000612.6(IGF2):​c.158-69C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 1,579,410 control chromosomes in the GnomAD database, including 7,237 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 0.12 (1787 hom., cov: 33)
  • Exomes 𝑓: 0.080 (5450 hom.)
• Consequence: IGF2 NM_000612.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 13 publications found

Genes affected

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]

ENSG00000284779 (HGNC:):

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000612.6. 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	NM_000612.6	MANE Select	c.158-69C>T		intron	N/A	NP_000603.1
	IGF2	NM_001127598.3		c.326-69C>T		intron	N/A	NP_001121070.1
	IGF2	NM_001007139.6		c.158-69C>T		intron	N/A	NP_001007140.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2	ENST00000416167.7	TSL:1 MANE Select	c.158-69C>T		intron	N/A	ENSP00000414497.2
	IGF2	ENST00000434045.6	TSL:1	c.326-69C>T		intron	N/A	ENSP00000391826.2
	IGF2	ENST00000381392.5	TSL:1	c.158-60C>T		intron	N/A	ENSP00000370799.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18936 AN: 152110 Hom.: 1781 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.0968

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0795

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.0801 AC: 114303 AN: 1427182 Hom.: 5450 AF XY: 0.0787 AC XY: 55808 AN XY: 708846

African (AFR) AF: 0.254 AC: 8198 AN: 32296

American (AMR) AF: 0.0599 AC: 2433 AN: 40590

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2684 AN: 25400

East Asian (EAS) AF: 0.000342 AC: 13 AN: 37984

South Asian (SAS) AF: 0.0467 AC: 3869 AN: 82912

European-Finnish (FIN) AF: 0.0795 AC: 4049 AN: 50910

Middle Eastern (MID) AF: 0.0810 AC: 368 AN: 4544

European-Non Finnish (NFE) AF: 0.0803 AC: 87769 AN: 1093636

Other (OTH) AF: 0.0835 AC: 4920 AN: 58910

GnomAD4 genome AF: 0.124 AC: 18943 AN: 152228 Hom.: 1787 Cov.: 33 AF XY: 0.122 AC XY: 9053 AN XY: 74458

African (AFR) AF: 0.254 AC: 10558 AN: 41500

American (AMR) AF: 0.0937 AC: 1434 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0968 AC: 336 AN: 3470

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5184

South Asian (SAS) AF: 0.0414 AC: 200 AN: 4826

European-Finnish (FIN) AF: 0.0795 AC: 843 AN: 10610

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5271 AN: 68010

Other (OTH) AF: 0.127 AC: 269 AN: 2114

Alfa AF: 0.0976 Hom.: 1026

Bravo AF: 0.135

Asia WGS AF: 0.0270 AC: 95 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.63
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3213232; hg19: chr11-2154964; COSMIC: COSV56098177; COSMIC: COSV56098177;