Variant chr11-2148654-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001042376.3(INS-IGF2):c.407+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

INS-IGF2
NM_001042376.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.869

Variant links:

Genes affected

INS-IGF2 (HGNC:33527): (INS-IGF2 readthrough) This locus includes two alternatively spliced read-through transcript variants which align to the INS gene in the 5' region and to the IGF2 gene in the 3' region. One transcript is predicted to encode a protein which shares the N-terminus with the INS protein but has a distinct and longer C-terminus, whereas the other transcript is a candidate for nonsense-mediated decay (NMD). The transcripts are imprinted and are paternally expressed in the limb and eye. [provided by RefSeq, Jul 2008]

INS-IGF2 links:

ENSG00000284779 (HGNC:):

ENSG00000284779 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:

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:

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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=-0.92).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	Protein	UniProt
INS-IGF2	NM_001042376.3 link	c.407+472G>T	intron_variant		NP_001035835.1	F8WCM5-1
IGF2	NM_001007139.6 link	c.-249+472G>T	intron_variant		NP_001007140.2	P01344-1
IGF2-AS	NR_028043.2 link	n.2056C>A	non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
INS-IGF2	ENST00000397270.1 link	c.407+472G>T		intron_variant		1		ENSP00000380440.1		F8WCM5-1
ENSG00000284779	ENST00000643349.2 link	c.254+472G>T		intron_variant				ENSP00000495715.1		A0A2R8Y747

Frequencies

GnomAD3 genomes

AF:

0.704

AC:

106766

AN:

151708

Hom.:

37865

Cov.:

show subpopulations

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.:

AF XY:

0.679

AC XY:

6492

AN XY:

9564

show subpopulations

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.:

AF XY:

0.701

AC XY:

52008

AN XY:

74180

show subpopulations

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

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