rs7984662

chr13-92271620-T-Cchr13-92271620-T-G

Variant summary

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

The NM_004466.6(GPC5):c.1561+126631T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,054 control chromosomes in the GnomAD database, including 6,649 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 0.29 (6649 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0420

Genes affected

GPC5 (HGNC:4453): (glypican 5) Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC5	NM_004466.6	c.1561+126631T>C		intron_variant		ENST00000377067.9
GPC5	XM_017020435.3	c.1561+126631T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+126631T>C		intron_variant		1	NM_004466.6	P1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44661 AN: 151936 Hom.: 6644 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.303

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44688 AN: 152054 Hom.: 6649 Cov.: 32 AF XY: 0.293 AC XY: 21747 AN XY: 74332

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.341

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.285

Gnomad4 OTH AF: 0.305

Alfa AF: 0.297 Hom.: 9347

Bravo AF: 0.297

Asia WGS AF: 0.337 AC: 1167 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.9
Dann	Benign	0.79

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: rs7984662; hg19: chr13-92923873;