6-160077933-C-T

Variant names:

• chr6-160077933-C-T
• rs8191898
• NM_000876.4:c.5317-268C>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.5317-268C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0883 in 152,216 control chromosomes in the GnomAD database, including 902 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 0.088 (902 hom., cov: 33)
• Consequence: IGF2R NM_000876.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.312 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.5317-268C>T		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.5317-268C>T		intron	N/A	ENSP00000349437.1
	IGF2R	ENST00000650503.1		n.1927-268C>T		intron	N/A
	IGF2R	ENST00000676781.1		n.*3425-268C>T		intron	N/A	ENSP00000504419.1

Frequencies

GnomAD3 genomes AF: 0.0881 AC: 13404 AN: 152098 Hom.: 893 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0690

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0499

Gnomad OTH AF: 0.0790

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

GnomAD4 genome AF: 0.0883 AC: 13436 AN: 152216 Hom.: 902 Cov.: 33 AF XY: 0.0909 AC XY: 6766 AN XY: 74404

African (AFR) AF: 0.109 AC: 4541 AN: 41524

American (AMR) AF: 0.153 AC: 2333 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3466

East Asian (EAS) AF: 0.325 AC: 1679 AN: 5164

South Asian (SAS) AF: 0.107 AC: 517 AN: 4828

European-Finnish (FIN) AF: 0.0690 AC: 731 AN: 10600

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0498 AC: 3390 AN: 68024

Other (OTH) AF: 0.0834 AC: 176 AN: 2110

Alfa AF: 0.0584 Hom.: 889

Bravo AF: 0.0988

Asia WGS AF: 0.220 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.61
PhyloP100		-0.41
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: rs8191898; hg19: chr6-160498965;