rs1127648

Positions:

• chr15-75674754-A-G
• chr15-75674754-A-T

Variant summary

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

The NM_001897.5(CSPG4):​c.*796T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 398,370 control chromosomes in the GnomAD database, including 55,532 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.51 (20094 hom., cov: 32)
  • Exomes 𝑓: 0.53 (35438 hom.)
• Consequence: CSPG4 NM_001897.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290

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 (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPG4	NM_001897.5	c.*796T>C		3_prime_UTR_variant	10/10	ENST00000308508.5
CSPG4	XM_047432196.1	c.*796T>C		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPG4	ENST00000308508.5	c.*796T>C		3_prime_UTR_variant	10/10	1	NM_001897.5	P1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77298 AN: 151818 Hom.: 20083 Cov.: 32

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.636

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.473

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.529 AC: 130468 AN: 246434 Hom.: 35438 Cov.: 0 AF XY: 0.531 AC XY: 66284 AN XY: 124896

Gnomad4 AFR exome AF: 0.421

Gnomad4 AMR exome AF: 0.545

Gnomad4 ASJ exome AF: 0.585

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.485

Gnomad4 FIN exome AF: 0.525

Gnomad4 NFE exome AF: 0.566

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.509 AC: 77343 AN: 151936 Hom.: 20094 Cov.: 32 AF XY: 0.505 AC XY: 37464 AN XY: 74258

Gnomad4 AFR AF: 0.423

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.518

Alfa AF: 0.557 Hom.: 32803

Bravo AF: 0.506

Asia WGS AF: 0.382 AC: 1333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.2
DANN	Benign	0.61

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: rs1127648; hg19: chr15-75967095;