Variant rs2028898 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 NM_000821.7(GGCX):c.2085-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 1,593,924 control chromosomes in the GnomAD database, including 62,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 6899 hom., cov: 31)

Exomes 𝑓: 0.27 ( 55582 hom. )

Consequence

GGCX
NM_000821.7 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.525

Variant links:

Genes affected

GGCX (HGNC:4247): (gamma-glutamyl carboxylase) This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

GGCX 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=-0.82).

BP6

Variant 2-85550147-G-A is Benign according to our data. Variant chr2-85550147-G-A is described in ClinVar as [Benign]. Clinvar id is 1278677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GGCX	NM_000821.7 linkuse as main transcript	c.2085-21C>T		intron_variant		ENST00000233838.9	NP_000812.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GGCX	ENST00000233838.9 linkuse as main transcript	c.2085-21C>T		intron_variant		1	NM_000821.7	ENSP00000233838	P1	P38435-1

Frequencies

GnomAD3 genomes

AF:

0.296

AC:

44990

AN:

151826

Hom.:

6887

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.326

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.262

AC:

64716

AN:

247468

Hom.:

8869

AF XY:

0.259

AC XY:

34763

AN XY:

134128

show subpopulations

Gnomad AFR exome

AF:

0.365

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.309

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.254

GnomAD4 exome

AF:

0.275

AC:

396002

AN:

1441980

Hom.:

55582

Cov.:

AF XY:

0.272

AC XY:

195212

AN XY:

718566

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.196

Gnomad4 ASJ exome

AF:

0.236

Gnomad4 EAS exome

AF:

0.312

Gnomad4 SAS exome

AF:

0.168

Gnomad4 FIN exome

AF:

0.301

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

AF:

0.296

AC:

45027

AN:

151944

Hom.:

6899

Cov.:

AF XY:

0.294

AC XY:

21860

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.360

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.326

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.283

Alfa

AF:

0.271

Hom.:

3677

Bravo

AF:

0.296

Asia WGS

AF:

0.278

AC:

966

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.0

DANN

Benign

0.73

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