13-92436398-T-C

Variant names:

• chr13-92436398-T-C
• rs4771859
• NM_004466.6:c.1561+291409T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004466.6(GPC5):​c.1561+291409T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,036 control chromosomes in the GnomAD database, including 29,674 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 0.62 (29674 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+291409T>C		intron_variant	Intron 7 of 7	ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1561+291409T>C		intron_variant	Intron 7 of 7		XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+291409T>C		intron_variant	Intron 7 of 7	1	NM_004466.6	ENSP00000366267.3

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94474 AN: 151918 Hom.: 29629 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.597

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.658

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.585

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

GnomAD4 genome AF: 0.622 AC: 94580 AN: 152036 Hom.: 29674 Cov.: 32 AF XY: 0.626 AC XY: 46534 AN XY: 74284

African (AFR) AF: 0.681 AC: 28252 AN: 41474

American (AMR) AF: 0.600 AC: 9160 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1774 AN: 3470

East Asian (EAS) AF: 0.737 AC: 3803 AN: 5160

South Asian (SAS) AF: 0.590 AC: 2845 AN: 4822

European-Finnish (FIN) AF: 0.658 AC: 6962 AN: 10584

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.587 AC: 39848 AN: 67942

Other (OTH) AF: 0.585 AC: 1235 AN: 2112

Alfa AF: 0.593 Hom.: 117971

Bravo AF: 0.622

Asia WGS AF: 0.671 AC: 2332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.30
DANN	Benign	0.62
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4771859; hg19: chr13-93088651;