rs3741208

chr11-2148544-A-Gchr11-2148544-A-T

Variant summary

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

The ENST00000643349.2(ENSG00000284779):c.254+582T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 153,680 control chromosomes in the GnomAD database, including 30,765 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 0.63 (30490 hom., cov: 32)
  • Exomes 𝑓: 0.55 (275 hom.)
• Consequence: ENST00000643349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IGF2-AS	NR_028043.2	n.1946A>G		non_coding_transcript_exon_variant	3/3
INS-IGF2	NR_003512.4	n.466+582T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000643349.2	c.254+582T>C		intron_variant				P1
IGF2-AS	ENST00000381361.4	n.1941A>G		non_coding_transcript_exon_variant	3/3	2
IGF2	ENST00000481781.3	c.-249+582T>C		intron_variant		5		P4
IGF2	ENST00000695541.1	c.-249+582T>C		intron_variant				P4

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95745 AN: 151810 Hom.: 30472 Cov.: 32

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.732

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.651

Gnomad NFE AF: 0.637

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.549 AC: 962 AN: 1752 Hom.: 275 Cov.: 0 AF XY: 0.560 AC XY: 493 AN XY: 880

Gnomad4 AFR exome AF: 0.591

Gnomad4 AMR exome AF: 0.414

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.745

Gnomad4 SAS exome AF: 0.600

Gnomad4 FIN exome AF: 0.372

Gnomad4 NFE exome AF: 0.552

Gnomad4 OTH exome AF: 0.518

GnomAD4 genome AF: 0.631 AC: 95795 AN: 151928 Hom.: 30490 Cov.: 32 AF XY: 0.629 AC XY: 46702 AN XY: 74266

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.637

Gnomad4 OTH AF: 0.631

Alfa AF: 0.631 Hom.: 38791

Bravo AF: 0.625

Asia WGS AF: 0.760 AC: 2643 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.0
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3741208; hg19: chr11-2169774;