15-75676580-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001897.5(CSPG4):c.5939G>A(p.Arg1980His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00396 in 1,613,092 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0041 (20 hom.)
• Consequence: CSPG4 NM_001897.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.452

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.012677461).
• BP6: Variant 15-75676580-C-T is Benign according to our data. Variant chr15-75676580-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2645568.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPG4	NM_001897.5	c.5939G>A	p.Arg1980His	missense_variant	10/10	ENST00000308508.5
CSPG4	XM_047432196.1	c.4877G>A	p.Arg1626His	missense_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPG4	ENST00000308508.5	c.5939G>A	p.Arg1980His	missense_variant	10/10	1	NM_001897.5	P1
	ENST00000569467.1	n.354C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.00288 AC: 438 AN: 152204 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00294

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00462

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00296 AC: 737 AN: 249124 Hom.: 2 AF XY: 0.00308 AC XY: 416 AN XY: 135062

Gnomad AFR exome AF: 0.000560

Gnomad AMR exome AF: 0.00217

Gnomad ASJ exome AF: 0.00389

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000785

Gnomad FIN exome AF: 0.000957

Gnomad NFE exome AF: 0.00489

Gnomad OTH exome AF: 0.00312

GnomAD4 exome AF: 0.00407 AC: 5942 AN: 1460770 Hom.: 20 Cov.: 32 AF XY: 0.00398 AC XY: 2893 AN XY: 726686

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00233

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000731

Gnomad4 FIN exome AF: 0.00187

Gnomad4 NFE exome AF: 0.00478

Gnomad4 OTH exome AF: 0.00369

GnomAD4 genome AF: 0.00288 AC: 438 AN: 152322 Hom.: 2 Cov.: 33 AF XY: 0.00250 AC XY: 186 AN XY: 74474

Gnomad4 AFR AF: 0.000769

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00462

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00431 Hom.: 3

Bravo AF: 0.00335

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00545 AC: 21

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00302 AC: 367

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2022

CSPG4: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.60
Cadd	Benign	12
Dann	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.030
Sift	Uncertain	0.016	D
Sift4G	Uncertain	0.035	D
Polyphen		0.022	B
Vest4		0.091
MVP		0.21
MPC		0.42
ClinPred		0.0084	T
GERP RS		0.60
Varity_R		0.053
gMVP		0.52

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: rs117177957; hg19: chr15-75968921; COSMIC: COSV99079504; COSMIC: COSV99079504;