13-93226778-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000610286.1(ENSG00000278177):n.540T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0368 in 152,140 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (149 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: ENST00000610286.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.691

Genes affected

(HGNC:):

GPC6 (HGNC:4454): (glypican 6) The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 13-93226778-A-G is Benign according to our data. Variant chr13-93226778-A-G is described in ClinVar as [Benign]. Clinvar id is 1257500.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPC6	XM_047429990.1	c.-51+96A>G		intron_variant
GPC6	NM_005708.5			upstream_gene_variant		ENST00000377047.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000610286.1	n.540T>C		non_coding_transcript_exon_variant	1/1
GPC6	ENST00000377047.9			upstream_gene_variant		1	NM_005708.5	P1

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5601 AN: 151928 Hom.: 149 Cov.: 32

Gnomad AFR AF: 0.0589

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0490

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0106 AC: 1 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.0179 AC XY: 1 AN XY: 56

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0208

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0369 AC: 5604 AN: 152046 Hom.: 149 Cov.: 32 AF XY: 0.0376 AC XY: 2794 AN XY: 74344

Gnomad4 AFR AF: 0.0588

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0409

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.00913

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0203

Gnomad4 OTH AF: 0.0308

Alfa AF: 0.0310 Hom.: 35

Bravo AF: 0.0390

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	0.53
Dann	Benign	0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7985891; hg19: chr13-93879031;