6-160107025-T-C

Variant names:

• chr6-160107025-T-C
• rs7753051
• NM_000876.4:c.*1941T>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.*1941T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,142 control chromosomes in the GnomAD database, including 7,906 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 0.31 (7906 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: IGF2R NM_000876.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGF2R	NM_000876.4	c.*1941T>C		3_prime_UTR_variant	Exon 48 of 48	ENST00000356956.6	NP_000867.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGF2R	ENST00000356956.6	c.*1941T>C		3_prime_UTR_variant	Exon 48 of 48	1	NM_000876.4	ENSP00000349437.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47094 AN: 152024 Hom.: 7887 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.287

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.310 AC: 47164 AN: 152142 Hom.: 7906 Cov.: 33 AF XY: 0.311 AC XY: 23109 AN XY: 74396

African (AFR) AF: 0.426 AC: 17689 AN: 41488

American (AMR) AF: 0.325 AC: 4976 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3466

East Asian (EAS) AF: 0.513 AC: 2658 AN: 5182

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4820

European-Finnish (FIN) AF: 0.239 AC: 2528 AN: 10582

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16606 AN: 67998

Other (OTH) AF: 0.288 AC: 609 AN: 2114

Alfa AF: 0.267 Hom.: 16702

Bravo AF: 0.325

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.62
PhyloP100		-0.14

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: rs7753051; hg19: chr6-160528057;