13-92270985-A-T

Position:

• chr13-92270985-A-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+125996A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 152,012 control chromosomes in the GnomAD database, including 16,449 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 0.44 (16449 hom., cov: 32)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+125996A>T		intron_variant		ENST00000377067.9	NP_004457.1
GPC5	XM_017020435.3	c.1561+125996A>T		intron_variant			XP_016875924.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+125996A>T		intron_variant		1	NM_004466.6	ENSP00000366267.3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67204 AN: 151894 Hom.: 16407 Cov.: 32

Gnomad AFR AF: 0.663

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.443 AC: 67299 AN: 152012 Hom.: 16449 Cov.: 32 AF XY: 0.437 AC XY: 32421 AN XY: 74270

Gnomad4 AFR AF: 0.663

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.379

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.440

Alfa AF: 0.382 Hom.: 1560

Bravo AF: 0.458

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.069
DANN	Benign	0.37

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: rs7996483; hg19: chr13-92923238;