Variant 13-93227137-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000377047.9(GPC6):c.-320C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 209,264 control chromosomes in the GnomAD database, including 2,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2048 hom., cov: 32)

Exomes 𝑓: 0.15 ( 758 hom. )

Consequence

GPC6
ENST00000377047.9 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.05

Variant links:

Genes affected

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]

GPC6 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 13-93227137-C-A is Benign according to our data. Variant chr13-93227137-C-A is described in ClinVar as [Benign]. Clinvar id is 312531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPC6	NM_005708.5 linkuse as main transcript	c.-320C>A		5_prime_UTR_variant	1/9	ENST00000377047.9	NP_005699.1
GPC6	XM_047429990.1 linkuse as main transcript	c.-51+455C>A		intron_variant			XP_047285946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPC6	ENST00000377047.9 linkuse as main transcript	c.-320C>A		5_prime_UTR_variant	1/9	1	NM_005708.5	ENSP00000366246	P1
	ENST00000610286.1 linkuse as main transcript	n.181G>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.153

AC:

23319

AN:

152072

Hom.:

2038

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0779

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.0660

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.152

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.170

GnomAD4 exome

AF:

0.147

AC:

8414

AN:

57076

Hom.:

758

Cov.:

AF XY:

0.148

AC XY:

4307

AN XY:

29084

show subpopulations

Gnomad4 AFR exome

AF:

0.0611

Gnomad4 AMR exome

AF:

0.200

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.0669

Gnomad4 SAS exome

AF:

0.0952

Gnomad4 FIN exome

AF:

0.128

Gnomad4 NFE exome

AF:

0.166

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.153

AC:

23351

AN:

152188

Hom.:

2048

Cov.:

AF XY:

0.152

AC XY:

11321

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0781

Gnomad4 AMR

AF:

0.216

Gnomad4 ASJ

AF:

0.137

Gnomad4 EAS

AF:

0.0655

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.152

Gnomad4 NFE

AF:

0.193

Gnomad4 OTH

AF:

0.175

Alfa

AF:

0.189

Hom.:

4687

Bravo

AF:

0.155

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive omodysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.79

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over