6-160077933-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.406
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IGF2RNM_000876.4 linkc.5317-268C>T intron_variant ENST00000356956.6 NP_000867.3 P11717

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IGF2RENST00000356956.6 linkc.5317-268C>T intron_variant 1 NM_000876.4 ENSP00000349437.1 P11717
IGF2RENST00000650503.1 linkn.1927-268C>T intron_variant
IGF2RENST00000676781.1 linkn.*3425-268C>T intron_variant ENSP00000504419.1 A0A7I2YQS7
IGF2RENST00000677704.1 linkn.*1188-268C>T intron_variant ENSP00000503314.1 A0A7I2V381

Frequencies

GnomAD3 genomes
AF:
0.0881
AC:
13404
AN:
152098
Hom.:
893
Cov.:
33
show subpopulations
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
show subpopulations
Gnomad4 AFR
AF:
0.109
Gnomad4 AMR
AF:
0.153
Gnomad4 ASJ
AF:
0.00548
Gnomad4 EAS
AF:
0.325
Gnomad4 SAS
AF:
0.107
Gnomad4 FIN
AF:
0.0690
Gnomad4 NFE
AF:
0.0498
Gnomad4 OTH
AF:
0.0834
Alfa
AF:
0.0552
Hom.:
593
Bravo
AF:
0.0988
Asia WGS
AF:
0.220
AC:
768
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.85
DANN
Benign
0.61

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8191898; hg19: chr6-160498965; API