dbSNP rs7985891: GPC6:c.-51+96A>G (chr13-93226778-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

ENSG00000278177
ENST00000610286.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.691

Publications

5 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive omodysplasia
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

GPC6 links:

ENSG00000278177 (HGNC:):

ENSG00000278177 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000610286.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 1257500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000610286.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPC6	NM_005708.5	MANE Select	c.-679A>G		upstream_gene	N/A	NP_005699.1	Q9Y625

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
ENSG00000278177	ENST00000610286.1	TSL:6	n.540T>C	non_coding_transcript_exon	Exon 1 of 1
ENSG00000302670	ENST00000788637.1		n.370+6396A>G	intron	N/A
ENSG00000302693	ENST00000788939.1		n.341-471T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

5601

AN:

151928

Hom.:

149

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0208

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0369

AC:

5604

AN:

152046

Hom.:

149

Cov.:

AF XY:

0.0376

AC XY:

2794

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0588

AC:

2438

AN:

41442

American (AMR)

AF:

0.0489

AC:

747

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0409

AC:

142

AN:

3468

East Asian (EAS)

AF:

0.0780

AC:

402

AN:

5156

South Asian (SAS)

AF:

0.00913

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0344

AC:

364

AN:

10582

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0203

AC:

1382

AN:

67992

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

270

540

810

1080

1350

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0268

Hom.:

138

Bravo

AF:

0.0390

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.53

(source)

DANN

Benign

0.69

PhyloP100

-0.69

PromoterAI

-0.099

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over