6-160001753-A-G

Variant names:

• chr6-160001753-A-G
• rs9295119
• NM_000876.4:c.290-7257A>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.290-7257A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 152,212 control chromosomes in the GnomAD database, including 3,574 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 0.20 (3574 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560
• Publications: 9 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.556 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.290-7257A>G		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.290-7257A>G		intron	N/A	ENSP00000349437.1
	IGF2R	ENST00000676781.1		n.290-7257A>G		intron	N/A	ENSP00000504419.1
	IGF2R	ENST00000677704.1		n.290-7257A>G		intron	N/A	ENSP00000503314.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29676 AN: 152094 Hom.: 3563 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.239

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.195 AC: 29706 AN: 152212 Hom.: 3574 Cov.: 32 AF XY: 0.207 AC XY: 15381 AN XY: 74418

African (AFR) AF: 0.202 AC: 8383 AN: 41534

American (AMR) AF: 0.239 AC: 3652 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3468

East Asian (EAS) AF: 0.573 AC: 2965 AN: 5172

South Asian (SAS) AF: 0.251 AC: 1212 AN: 4820

European-Finnish (FIN) AF: 0.284 AC: 3010 AN: 10592

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9641 AN: 68008

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.158 Hom.: 9727

Bravo AF: 0.195

Asia WGS AF: 0.411 AC: 1431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.6
DANN	Benign	0.59
PhyloP100		0.056
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: rs9295119; hg19: chr6-160422785;