13-92490453-T-C

Variant names:

• chr13-92490453-T-C
• rs6492611
• NM_004466.6:c.1561+345464T>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+345464T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 151,886 control chromosomes in the GnomAD database, including 45,568 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 0.77 (45568 hom., cov: 31)
• Consequence: GPC5 NM_004466.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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]

GPC5-IT1 (HGNC:41340): (GPC5 intronic transcript 1)

MIR548AS (HGNC:43550): (microRNA 548as) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPC5	NM_004466.6	c.1561+345464T>C		intron_variant	Intron 7 of 7	ENST00000377067.9	NP_004457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPC5	ENST00000377067.9	c.1561+345464T>C		intron_variant	Intron 7 of 7	1	NM_004466.6	ENSP00000366267.3
GPC5-IT1	ENST00000416664.1	n.76+5772T>C		intron_variant	Intron 1 of 1	3
MIR548AS	ENST00000579177.1	n.*233T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117527 AN: 151768 Hom.: 45517 Cov.: 31

Gnomad AFR AF: 0.794

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.780

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.751

Gnomad OTH AF: 0.794

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

GnomAD4 genome AF: 0.774 AC: 117630 AN: 151886 Hom.: 45568 Cov.: 31 AF XY: 0.778 AC XY: 57749 AN XY: 74232

African (AFR) AF: 0.794 AC: 32928 AN: 41456

American (AMR) AF: 0.805 AC: 12266 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2913 AN: 3472

East Asian (EAS) AF: 0.798 AC: 4119 AN: 5160

South Asian (SAS) AF: 0.780 AC: 3766 AN: 4826

European-Finnish (FIN) AF: 0.761 AC: 8036 AN: 10564

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.751 AC: 50987 AN: 67852

Other (OTH) AF: 0.796 AC: 1679 AN: 2110

Alfa AF: 0.764 Hom.: 133223

Bravo AF: 0.778

Asia WGS AF: 0.795 AC: 2761 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.4
DANN	Benign	0.77
PhyloP100		0.21
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: rs6492611; hg19: chr13-93142706;