6-160070709-A-G

Variant names:

• chr6-160070709-A-G
• rs3798180
• NM_000876.4:c.4443+651A>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.4443+651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,968 control chromosomes in the GnomAD database, including 16,935 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 0.46 (16935 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 11 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	NM_000876.4	MANE Select	c.4443+651A>G		intron	N/A	NP_000867.3	P11717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGF2R	ENST00000356956.6	TSL:1 MANE Select	c.4443+651A>G		intron	N/A	ENSP00000349437.1	P11717
	IGF2R	ENST00000650503.1		n.1053+651A>G		intron	N/A
	IGF2R	ENST00000676781.1		n.*2551+651A>G		intron	N/A	ENSP00000504419.1	A0A7I2YQS7

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69887 AN: 151850 Hom.: 16893 Cov.: 32

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.455

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

GnomAD4 genome AF: 0.460 AC: 69979 AN: 151968 Hom.: 16935 Cov.: 32 AF XY: 0.460 AC XY: 34188 AN XY: 74278

African (AFR) AF: 0.598 AC: 24798 AN: 41438

American (AMR) AF: 0.449 AC: 6857 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.670 AC: 3442 AN: 5136

South Asian (SAS) AF: 0.470 AC: 2266 AN: 4820

European-Finnish (FIN) AF: 0.364 AC: 3843 AN: 10560

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25973 AN: 67956

Other (OTH) AF: 0.460 AC: 971 AN: 2110

Alfa AF: 0.415 Hom.: 17418

Bravo AF: 0.476

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.075
DANN	Benign	0.21
PhyloP100		-1.3
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: rs3798180; hg19: chr6-160491741; COSMIC: COSV63627624; COSMIC: COSV63627624;