rs4244809

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153

Genes affected

(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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
INS-IGF2	NR_003512.4	n.708+4463C>T		intron_variant, non_coding_transcript_variant
IGF2-AS	NR_028043.2	n.436+2156G>A		intron_variant, non_coding_transcript_variant
IGF2	NM_001007139.6	c.-7+4463C>T		intron_variant			NP_001007140.2
IGF2-AS	NR_133657.1	n.436+2156G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000643349.2	c.*46+4463C>T		intron_variant				ENSP00000495715	P1
IGF2-AS	ENST00000381361.4	n.431+2156G>A		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.215

Gnomad4 OTH AF: 0.229

Alfa AF: 0.180 Hom.: 488

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4244809; hg19: chr11-2164333;