rs76827801
Positions:
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1
The NM_001897.5(CSPG4):c.914C>T(p.Thr305Met) variant causes a missense change. The variant allele was found at a frequency of 0.00903 in 142,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0090 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0048 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CSPG4
NM_001897.5 missense
NM_001897.5 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 5.15
Genes affected
CSPG4 (HGNC:2466): (chondroitin sulfate proteoglycan 4) A human melanoma-associated chondroitin sulfate proteoglycan plays a role in stabilizing cell-substratum interactions during early events of melanoma cell spreading on endothelial basement membranes. CSPG4 represents an integral membrane chondroitin sulfate proteoglycan expressed by human malignant melanoma cells. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
PM2
Variant has high frequency in the AFR(0.0608651) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).
BP4
Computational evidence support a benign effect (MetaRNN=0.003302157).
BP6
Variant 15-75690151-G-A is Benign according to our data. Variant chr15-75690151-G-A is described in ClinVar as [Benign]. Clinvar id is 402567.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00903 (1290/142802) while in subpopulation AFR AF= 0.0313 (1065/34032). AF 95% confidence interval is 0.0297. There are 0 homozygotes in gnomad4. There are 637 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSPG4 | NM_001897.5 | c.914C>T | p.Thr305Met | missense_variant | 3/10 | ENST00000308508.5 | |
CSPG4 | XM_047432196.1 | c.-149C>T | 5_prime_UTR_variant | 3/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSPG4 | ENST00000308508.5 | c.914C>T | p.Thr305Met | missense_variant | 3/10 | 1 | NM_001897.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00900 AC: 1284AN: 142732Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00786 AC: 1926AN: 244940Hom.: 0 AF XY: 0.00666 AC XY: 887AN XY: 133140
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00477 AC: 6847AN: 1435236Hom.: 0 Cov.: 34 AF XY: 0.00465 AC XY: 3320AN XY: 714496
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.00903 AC: 1290AN: 142802Hom.: 0 Cov.: 33 AF XY: 0.00911 AC XY: 637AN XY: 69902
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 28, 2016 | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at