rs3798176

Variant names:

• chr6-160087140-T-C
• rs3798176
• NM_000876.4:c.6206-893T>C

Variant summary

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

The NM_000876.4(IGF2R):​c.6206-893T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,986 control chromosomes in the GnomAD database, including 16,175 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 0.45 (16175 hom., cov: 32)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.45
• Publications: 8 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=-1.03).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.6206-893T>C		intron_variant	Intron 41 of 47	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.6206-893T>C		intron_variant	Intron 41 of 47	1	NM_000876.4	ENSP00000349437.1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68451 AN: 151868 Hom.: 16131 Cov.: 32

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.446

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.445

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

GnomAD4 genome AF: 0.451 AC: 68542 AN: 151986 Hom.: 16175 Cov.: 32 AF XY: 0.451 AC XY: 33497 AN XY: 74264

African (AFR) AF: 0.569 AC: 23589 AN: 41426

American (AMR) AF: 0.446 AC: 6810 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1312 AN: 3464

East Asian (EAS) AF: 0.670 AC: 3457 AN: 5162

South Asian (SAS) AF: 0.467 AC: 2252 AN: 4818

European-Finnish (FIN) AF: 0.363 AC: 3832 AN: 10566

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25827 AN: 67956

Other (OTH) AF: 0.451 AC: 953 AN: 2112

Alfa AF: 0.408 Hom.: 21321

Bravo AF: 0.465

Asia WGS AF: 0.599 AC: 2082 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	0.030
DANN	Benign	0.17
PhyloP100		-2.5
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: rs3798176; hg19: chr6-160508172;