Variant rs1003483 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Variant links:

Genes affected

(HGNC:):

links:

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-AS links:

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]

IGF2 links:

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ACMG classification

Classification made for transcript

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	Effect	#exon/exons	Protein
IGF2-AS	NR_028043.2 linkuse as main transcript	n.505T>G	non_coding_transcript_exon_variant	2/3
INS-IGF2	NR_003512.4 linkuse as main transcript	n.708+1253A>C	intron_variant, non_coding_transcript_variant
IGF2	NM_001007139.6 linkuse as main transcript	c.-7+1253A>C	intron_variant		NP_001007140.2
IGF2-AS	NR_133657.1 linkuse as main transcript	n.437-43T>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000643349.2 linkuse as main transcript	c.*46+1253A>C		intron_variant				ENSP00000495715	P1
IGF2-AS	ENST00000381361.4 linkuse as main transcript	n.500T>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.399

AC:

60682

AN:

152048

Hom.:

13946

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.459

AC XY:

100368

AN XY:

218456

show subpopulations

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.:

AF XY:

0.405

AC XY:

30143

AN XY:

74392

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over