rs6917747

Variant names:

• chr6-159981673-G-A
• rs6917747
• NM_000876.4:c.150-9511G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000876.4(IGF2R):​c.150-9511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 152,272 control chromosomes in the GnomAD database, including 1,033 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 0.11 (1033 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000876.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	NM_000876.4	MANE Select	c.150-9511G>A		intron	N/A	NP_000867.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	ENST00000356956.6	TSL:1 MANE Select	c.150-9511G>A		intron	N/A	ENSP00000349437.1
	IGF2R	ENST00000676781.1		n.150-9511G>A		intron	N/A	ENSP00000504419.1
	IGF2R	ENST00000677704.1		n.150-9511G>A		intron	N/A	ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.107 AC: 16279 AN: 152154 Hom.: 1027 Cov.: 33

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.0809

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.0279

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.107 AC: 16317 AN: 152272 Hom.: 1033 Cov.: 33 AF XY: 0.107 AC XY: 7985 AN XY: 74442

African (AFR) AF: 0.0555 AC: 2308 AN: 41576

American (AMR) AF: 0.0806 AC: 1234 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3468

East Asian (EAS) AF: 0.0282 AC: 146 AN: 5182

South Asian (SAS) AF: 0.142 AC: 685 AN: 4826

European-Finnish (FIN) AF: 0.138 AC: 1462 AN: 10606

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9391 AN: 67994

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.127 Hom.: 6056

Bravo AF: 0.0976

Asia WGS AF: 0.0850 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.66
PhyloP100		0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6917747; hg19: chr6-160402705;