13-91718836-A-G

Variant names:

• chr13-91718836-A-G
• rs462954
• NM_004466.6:c.1021-9696A>G

Variant summary

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

The NM_004466.6(GPC5):​c.1021-9696A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 151,968 control chromosomes in the GnomAD database, including 2,216 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 0.16 (2216 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004466.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC5	NM_004466.6	MANE Select	c.1021-9696A>G		intron	N/A	NP_004457.1	P78333

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC5	ENST00000377067.9	TSL:1 MANE Select	c.1021-9696A>G		intron	N/A	ENSP00000366267.3	P78333

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24085 AN: 151850 Hom.: 2211 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.0993

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.159 AC: 24119 AN: 151968 Hom.: 2216 Cov.: 32 AF XY: 0.160 AC XY: 11861 AN XY: 74292

African (AFR) AF: 0.222 AC: 9178 AN: 41418

American (AMR) AF: 0.179 AC: 2731 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3468

East Asian (EAS) AF: 0.349 AC: 1791 AN: 5128

South Asian (SAS) AF: 0.156 AC: 754 AN: 4818

European-Finnish (FIN) AF: 0.0993 AC: 1050 AN: 10570

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7630 AN: 67980

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.127 Hom.: 2947

Bravo AF: 0.169

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.7
DANN	Benign	0.75
PhyloP100		0.36
Mutation Taster		=99/1	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: rs462954; hg19: chr13-92371090;