Variant 15-75677729-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000308508.5(CSPG4):c.5108G>A(p.Arg1703His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 1,604,012 control chromosomes in the GnomAD database, including 119,864 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.33 ( 8900 hom., cov: 32)

Exomes 𝑓: 0.38 ( 110964 hom. )

Consequence

CSPG4
ENST00000308508.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.68

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:

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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 (MetaRNN=0.0016655624).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.396 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPG4	NM_001897.5 linkuse as main transcript	c.5108G>A	p.Arg1703His	missense_variant	9/10	ENST00000308508.5	NP_001888.2
CSPG4	XM_047432196.1 linkuse as main transcript	c.4046G>A	p.Arg1349His	missense_variant	9/10		XP_047288152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPG4	ENST00000308508.5 linkuse as main transcript	c.5108G>A	p.Arg1703His	missense_variant	9/10	1	NM_001897.5	ENSP00000312506	P1

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50073

AN:

151942

Hom.:

8893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.358

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.416

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.256

Gnomad FIN

AF:

0.385

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.328

GnomAD3 exomes

AF:

0.346

AC:

83510

AN:

241124

Hom.:

15380

AF XY:

0.347

AC XY:

45475

AN XY:

131010

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.422

Gnomad EAS exome

AF:

0.200

Gnomad SAS exome

AF:

0.267

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.411

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.385

AC:

558819

AN:

1451952

Hom.:

110964

Cov.:

AF XY:

0.382

AC XY:

275882

AN XY:

722386

show subpopulations

Gnomad4 AFR exome

AF:

0.191

Gnomad4 AMR exome

AF:

0.311

Gnomad4 ASJ exome

AF:

0.416

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.270

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.411

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.329

AC:

50085

AN:

152060

Hom.:

8900

Cov.:

AF XY:

0.326

AC XY:

24235

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.416

Gnomad4 EAS

AF:

0.181

Gnomad4 SAS

AF:

0.255

Gnomad4 FIN

AF:

0.385

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.326

Alfa

AF:

0.378

Hom.:

12821

Bravo

AF:

0.320

TwinsUK

AF:

0.409

AC:

1518

ALSPAC

AF:

0.411

AC:

1583

ESP6500AA

AF:

0.202

AC:

887

ESP6500EA

AF:

0.400

AC:

3435

ExAC

AF:

0.346

AC:

42068

Asia WGS

AF:

0.225

AC:

785

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.9

MutationTaster

Benign

0.0099

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

REVEL

Benign

0.025

Sift

Benign

0.061

Sift4G

Benign

0.11

Polyphen

0.0020

Vest4

0.10

MPC

0.41

ClinPred

0.016

GERP RS

3.1

Varity_R

0.075

gMVP

0.56

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over