rs10945645

Variant names:

• chr6-159984392-G-A
• rs10945645
• NM_000876.4:c.150-6792G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-159984392-G-A
• chr6-159984392-G-T

Variant summary

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

The NM_000876.4(IGF2R):​c.150-6792G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,096 control chromosomes in the GnomAD database, including 2,891 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 0.18 (2891 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.150-6792G>A		intron_variant	Intron 1 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.150-6792G>A		intron_variant	Intron 1 of 47	1	NM_000876.4	ENSP00000349437.1
IGF2R	ENST00000676781.1	n.150-6792G>A		intron_variant	Intron 1 of 48			ENSP00000504419.1
IGF2R	ENST00000677704.1	n.150-6792G>A		intron_variant	Intron 1 of 48			ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 26995 AN: 151978 Hom.: 2879 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.0699

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.160

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

GnomAD4 genome AF: 0.178 AC: 27034 AN: 152096 Hom.: 2891 Cov.: 32 AF XY: 0.187 AC XY: 13912 AN XY: 74352

African (AFR) AF: 0.207 AC: 8595 AN: 41474

American (AMR) AF: 0.223 AC: 3407 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0699 AC: 242 AN: 3464

East Asian (EAS) AF: 0.456 AC: 2366 AN: 5184

South Asian (SAS) AF: 0.151 AC: 727 AN: 4826

European-Finnish (FIN) AF: 0.268 AC: 2825 AN: 10556

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8395 AN: 67998

Other (OTH) AF: 0.167 AC: 352 AN: 2112

Alfa AF: 0.123 Hom.: 682

Bravo AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.50
PhyloP100		0.53
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: rs10945645; hg19: chr6-160405424;