rs8191818

Variant names:

• chr6-160050159-T-G
• rs8191818
• NM_000876.4:c.2515-314T>G

Variant summary

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

The NM_000876.4(IGF2R):​c.2515-314T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,212 control chromosomes in the GnomAD database, including 1,177 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 0.10 (1177 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 3 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.2515-314T>G		intron_variant	Intron 18 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.2515-314T>G		intron_variant	Intron 18 of 47	1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000676781.1	n.*623-314T>G		intron_variant	Intron 19 of 48			ENSP00000504419.1
IGF2R	ENST00000677704.1	n.2515-314T>G		intron_variant	Intron 18 of 48			ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15354 AN: 152094 Hom.: 1167 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0876

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

GnomAD4 genome AF: 0.101 AC: 15389 AN: 152212 Hom.: 1177 Cov.: 32 AF XY: 0.103 AC XY: 7656 AN XY: 74418

African (AFR) AF: 0.154 AC: 6416 AN: 41530

American (AMR) AF: 0.156 AC: 2385 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.324 AC: 1674 AN: 5174

South Asian (SAS) AF: 0.107 AC: 519 AN: 4828

European-Finnish (FIN) AF: 0.0690 AC: 732 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0500 AC: 3398 AN: 68006

Other (OTH) AF: 0.0919 AC: 194 AN: 2112

Alfa AF: 0.0730 Hom.: 321

Bravo AF: 0.113

Asia WGS AF: 0.223 AC: 779 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		-0.21
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: rs8191818; hg19: chr6-160471191;