rs1003737

Positions:

• chr6-160009624-A-C
• chr6-160009624-A-T

Variant summary

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

The NM_000876.4(IGF2R):​c.414+490A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,008 control chromosomes in the GnomAD database, including 18,591 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 0.49 (18591 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35

Genes affected

IGF2R (HGNC:5467): (insulin like growth factor 2 receptor) This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]

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 (EAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.414+490A>C		intron_variant		ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.414+490A>C		intron_variant		1	NM_000876.4	ENSP00000349437	P1
IGF2R	ENST00000676781.1	c.414+490A>C		intron_variant, NMD_transcript_variant				ENSP00000504419
IGF2R	ENST00000677704.1	c.414+490A>C		intron_variant, NMD_transcript_variant				ENSP00000503314

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74393 AN: 151890 Hom.: 18549 Cov.: 33

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.425

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.464

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.490 AC: 74489 AN: 152008 Hom.: 18591 Cov.: 33 AF XY: 0.499 AC XY: 37053 AN XY: 74294

Gnomad4 AFR AF: 0.521

Gnomad4 AMR AF: 0.462

Gnomad4 ASJ AF: 0.425

Gnomad4 EAS AF: 0.714

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.470

Alfa AF: 0.443 Hom.: 19558

Bravo AF: 0.482

Asia WGS AF: 0.595 AC: 2065 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1003737; hg19: chr6-160430656;