rs8023621

chr15-75677729-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001897.5(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. 12/19 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 NM_001897.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.68

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]

ACMG classification

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	UniProt
CSPG4	NM_001897.5	c.5108G>A	p.Arg1703His	missense_variant	9/10	ENST00000308508.5
CSPG4	XM_047432196.1	c.4046G>A	p.Arg1349His	missense_variant	9/10

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50073 AN: 151942 Hom.: 8893 Cov.: 32

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

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.: 45 AF XY: 0.382 AC XY: 275882 AN XY: 722386

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.: 32 AF XY: 0.326 AC XY: 24235 AN XY: 74366

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	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	20
Dann	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.0099	P
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.025
Sift	Benign	0.061	T
Sift4G	Benign	0.11	T
Polyphen		0.0020	B
Vest4		0.10
MPC		0.41
ClinPred		0.016	T
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

Other links and lift over

dbSNP: rs8023621; hg19: chr15-75970070; COSMIC: COSV57892403; COSMIC: COSV57892403;