rs4244809

Variant names:

• chr11-2143103-G-A
• rs4244809
• ENST00000643349.2:c.*46+4463C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-2143103-G-A
• chr11-2143103-G-C
• chr11-2143103-G-T

Variant summary

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

The ENST00000643349.2(ENSG00000284779):​c.*46+4463C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,082 control chromosomes in the GnomAD database, including 3,530 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 0.19 (3530 hom., cov: 31)
• Consequence: ENSG00000284779 ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 12 publications found

Genes affected

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]

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]

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2	NM_001007139.6	c.-7+4463C>T		intron_variant	Intron 2 of 4		NP_001007140.2
INS-IGF2	NR_003512.4	n.708+4463C>T		intron_variant	Intron 4 of 6
IGF2-AS	NR_028043.2	n.436+2156G>A		intron_variant	Intron 1 of 2
IGF2-AS	NR_133657.1	n.436+2156G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000284779	ENST00000643349.2	c.*46+4463C>T		intron_variant	Intron 2 of 4			ENSP00000495715.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29460 AN: 151964 Hom.: 3534 Cov.: 31

Gnomad AFR AF: 0.0861

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.528

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.194 AC: 29446 AN: 152082 Hom.: 3530 Cov.: 31 AF XY: 0.200 AC XY: 14867 AN XY: 74346

African (AFR) AF: 0.0860 AC: 3566 AN: 41484

American (AMR) AF: 0.178 AC: 2726 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.528 AC: 2722 AN: 5154

South Asian (SAS) AF: 0.469 AC: 2258 AN: 4816

European-Finnish (FIN) AF: 0.190 AC: 2008 AN: 10576

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14637 AN: 67988

Other (OTH) AF: 0.229 AC: 483 AN: 2112

Alfa AF: 0.177 Hom.: 490

Bravo AF: 0.185

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.9
DANN	Benign	0.65
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4244809; hg19: chr11-2164333;