13-92270985-A-T

Variant names:

• chr13-92270985-A-T
• rs7996483
• NM_004466.6:c.1561+125996A>T

Variant summary

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

The ENST00000377067.9(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 ENST00000377067.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377067.9. 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+125996A>T		intron	N/A	NP_004457.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC5	ENST00000377067.9	TSL:1 MANE Select	c.1561+125996A>T		intron	N/A	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

African (AFR) AF: 0.663 AC: 27506 AN: 41476

American (AMR) AF: 0.374 AC: 5704 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1956 AN: 5156

South Asian (SAS) AF: 0.436 AC: 2102 AN: 4820

European-Finnish (FIN) AF: 0.269 AC: 2842 AN: 10562

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.356 AC: 24197 AN: 67956

Other (OTH) AF: 0.440 AC: 926 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.069
DANN	Benign	0.37
PhyloP100		-3.2
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: rs7996483; hg19: chr13-92923238;