rs1003483

Positions:

• chr11-2146313-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000643349.2(ENSG00000284779):​c.*46+1253A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 535,818 control chromosomes in the GnomAD database, including 58,442 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 0.40 (13961 hom., cov: 34)
  • Exomes 𝑓: 0.47 (44481 hom.)
• Consequence: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2-AS	NR_028043.2	n.505T>G		non_coding_transcript_exon_variant	2/3
INS-IGF2	NR_003512.4	n.708+1253A>C		intron_variant, non_coding_transcript_variant
IGF2	NM_001007139.6	c.-7+1253A>C		intron_variant
IGF2-AS	NR_133657.1	n.437-43T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000643349.2	c.*46+1253A>C		intron_variant				P1
IGF2-AS	ENST00000381361.4	n.500T>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60682 AN: 152048 Hom.: 13946 Cov.: 34

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.461

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.415

GnomAD3 exomes AF: 0.465 AC: 115517 AN: 248336 Hom.: 28789 AF XY: 0.459 AC XY: 61951 AN XY: 134876

Gnomad AFR exome AF: 0.161

Gnomad AMR exome AF: 0.637

Gnomad ASJ exome AF: 0.448

Gnomad EAS exome AF: 0.356

Gnomad SAS exome AF: 0.353

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.483

Gnomad OTH exome AF: 0.469

GnomAD4 exome AF: 0.469 AC: 180029 AN: 383652 Hom.: 44481 Cov.: 0 AF XY: 0.459 AC XY: 100368 AN XY: 218456

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.634

Gnomad4 ASJ exome AF: 0.447

Gnomad4 EAS exome AF: 0.368

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.577

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.449

GnomAD4 genome AF: 0.399 AC: 60714 AN: 152166 Hom.: 13961 Cov.: 34 AF XY: 0.405 AC XY: 30143 AN XY: 74392

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.461

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.414

Alfa AF: 0.464 Hom.: 19284

Bravo AF: 0.387

Asia WGS AF: 0.360 AC: 1249 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1003483; hg19: chr11-2167543; COSMIC: COSV56097715; COSMIC: COSV56097715;