rs3741205

Positions:

• chr11-2148654-C-A
• chr11-2148654-C-T

Variant summary

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

The ENST00000643349.2(ENSG00000284779):​c.254+472G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 170,946 control chromosomes in the GnomAD database, including 42,630 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 0.70 (37911 hom., cov: 31)
  • Exomes 𝑓: 0.69 (4719 hom.)
• Consequence: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.869

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2-AS	NR_028043.2	n.2056C>A		non_coding_transcript_exon_variant	3/3
INS-IGF2	NR_003512.4	n.466+472G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000643349.2	c.254+472G>T		intron_variant				P1
IGF2-AS	ENST00000381361.4	n.2051C>A		non_coding_transcript_exon_variant	3/3	2
IGF2	ENST00000481781.3	c.-249+472G>T		intron_variant		5		P4
IGF2	ENST00000695541.1	c.-249+472G>T		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106766 AN: 151708 Hom.: 37865 Cov.: 31

Gnomad AFR AF: 0.671

Gnomad AMI AF: 0.933

Gnomad AMR AF: 0.756

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.689 AC: 13174 AN: 19120 Hom.: 4719 Cov.: 0 AF XY: 0.679 AC XY: 6492 AN XY: 9564

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.760

Gnomad4 ASJ exome AF: 0.628

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.501

Gnomad4 FIN exome AF: 0.733

Gnomad4 NFE exome AF: 0.720

Gnomad4 OTH exome AF: 0.705

GnomAD4 genome AF: 0.704 AC: 106872 AN: 151826 Hom.: 37911 Cov.: 31 AF XY: 0.701 AC XY: 52008 AN XY: 74180

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.757

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.754

Gnomad4 NFE AF: 0.733

Gnomad4 OTH AF: 0.676

Alfa AF: 0.715 Hom.: 37963

Bravo AF: 0.703

Asia WGS AF: 0.547 AC: 1903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.59
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3741205; hg19: chr11-2169884;