rs4771856

chr13-92342256-C-Achr13-92342256-C-T

Variant summary

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

The NM_004466.6(GPC5):c.1561+197267C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 151,954 control chromosomes in the GnomAD database, including 6,482 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 (6482 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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]

GPC5-AS2 (HGNC:39887): (GPC5 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC5	NM_004466.6	c.1561+197267C>A		intron_variant		ENST00000377067.9
GPC5-AS2	NR_120382.1	n.221+316G>T		intron_variant, non_coding_transcript_variant
GPC5	XM_017020435.3	c.1561+197267C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+197267C>A		intron_variant		1	NM_004466.6	P1
GPC5-AS2	ENST00000656007.1	n.386+316G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43600 AN: 151836 Hom.: 6469 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.287 AC: 43650 AN: 151954 Hom.: 6482 Cov.: 32 AF XY: 0.286 AC XY: 21223 AN XY: 74286

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.356

Gnomad4 SAS AF: 0.396

Gnomad4 FIN AF: 0.190

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.292

Alfa AF: 0.268 Hom.: 7430

Bravo AF: 0.291

Asia WGS AF: 0.342 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.99
Dann	Benign	0.41

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: rs4771856; hg19: chr13-92994509;