6-160080675-C-T

Position:

• chr6-160080675-C-T

Variant summary

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

The NM_000876.4(IGF2R):​c.5833+400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,822 control chromosomes in the GnomAD database, including 14,584 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 0.43 (14584 hom., cov: 31)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.799

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 = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.5833+400C>T		intron_variant		ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.5833+400C>T		intron_variant		1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000650503.1	n.2443+400C>T		intron_variant
IGF2R	ENST00000676781.1	n.*3941+400C>T		intron_variant				ENSP00000504419.1
IGF2R	ENST00000677704.1	n.*1704+400C>T		intron_variant				ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65401 AN: 151704 Hom.: 14546 Cov.: 31

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.431 AC: 65485 AN: 151822 Hom.: 14584 Cov.: 31 AF XY: 0.432 AC XY: 32092 AN XY: 74218

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.359

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.440

Alfa AF: 0.373 Hom.: 4105

Bravo AF: 0.444

Asia WGS AF: 0.592 AC: 2058 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	0.10
DANN	Benign	0.65

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: rs2282141; hg19: chr6-160501707; COSMIC: COSV63627641; COSMIC: COSV63627641;