rs76827801

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.15

Variant links:

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]

CSPG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CSPG4	NM_001897.5 link	c.914C>T	p.Thr305Met	missense_variant	Exon 3 of 10	ENST00000308508.5	NP_001888.2	Q6UVK1
CSPG4	XM_047432196.1 link	c.-149C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 3 of 10		XP_047288152.1
CSPG4	XM_047432196.1 link	c.-149C>T		5_prime_UTR_variant	Exon 3 of 10		XP_047288152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPG4	ENST00000308508.5 link	c.914C>T	p.Thr305Met	missense_variant	Exon 3 of 10	1	NM_001897.5	ENSP00000312506.5		Q6UVK1

Frequencies

GnomAD3 genomes

AF:

0.00900

AC:

1284

AN:

142732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0312

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00399

Gnomad ASJ

AF:

0.00293

Gnomad EAS

AF:

0.000775

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.000663

Gnomad MID

AF:

0.00685

Gnomad NFE

AF:

0.00179

Gnomad OTH

AF:

0.00914

GnomAD3 exomes

AF:

0.00786

AC:

1926

AN:

244940

Hom.:

AF XY:

0.00666

AC XY:

887

AN XY:

133140

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.00501

Gnomad ASJ exome

AF:

0.00394

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.00187

Gnomad FIN exome

AF:

0.00227

Gnomad NFE exome

AF:

0.00526

Gnomad OTH exome

AF:

0.00502

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00477

AC:

6847

AN:

1435236

Hom.:

Cov.:

AF XY:

0.00465

AC XY:

3320

AN XY:

714496

show subpopulations

Gnomad4 AFR exome

AF:

0.0634

Gnomad4 AMR exome

AF:

0.00382

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.000462

Gnomad4 SAS exome

AF:

0.00116

Gnomad4 FIN exome

AF:

0.00145

Gnomad4 NFE exome

AF:

0.00393

Gnomad4 OTH exome

AF:

0.00549

GnomAD4 genome

AF:

0.00903

AC:

1290

AN:

142802

Hom.:

Cov.:

AF XY:

0.00911

AC XY:

637

AN XY:

69902

show subpopulations

Gnomad4 AFR

AF:

0.0313

Gnomad4 AMR

AF:

0.00398

Gnomad4 ASJ

AF:

0.00293

Gnomad4 EAS

AF:

0.000777

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000663

Gnomad4 NFE

AF:

0.00179

Gnomad4 OTH

AF:

0.00904

Alfa

AF:

0.0138

Hom.:

ExAC

AF:

0.0206

AC:

2502

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0033

MetaSVM

Uncertain

-0.013

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.50

Sift

Uncertain

0.014

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.24

MPC

0.91

ClinPred

0.015

GERP RS

5.3

Varity_R

0.079

gMVP

0.62

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over