chr13-92342256-C-A

Variant names:

• chr13-92342256-C-A
• rs4771856
• NM_004466.6:c.1561+197267C>A

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+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
• Publications: 4 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]

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

ACMG classification

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC5	NM_004466.6	MANE Select	c.1561+197267C>A		intron	N/A	NP_004457.1
	GPC5-AS2	NR_120382.1		n.221+316G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC5	ENST00000377067.9	TSL:1 MANE Select	c.1561+197267C>A		intron	N/A	ENSP00000366267.3
	GPC5-AS2	ENST00000656007.1		n.386+316G>T		intron	N/A
	GPC5-AS2	ENST00000810843.1		n.381+316G>T		intron	N/A

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

African (AFR) AF: 0.336 AC: 13909 AN: 41422

American (AMR) AF: 0.278 AC: 4243 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 917 AN: 3472

East Asian (EAS) AF: 0.356 AC: 1839 AN: 5164

South Asian (SAS) AF: 0.396 AC: 1910 AN: 4820

European-Finnish (FIN) AF: 0.190 AC: 2012 AN: 10588

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.263 AC: 17878 AN: 67942

Other (OTH) AF: 0.292 AC: 614 AN: 2102

Alfa AF: 0.272 Hom.: 10645

Bravo AF: 0.291

Asia WGS AF: 0.342 AC: 1186 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.41
PhyloP100		-0.18
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: rs4771856; hg19: chr13-92994509;