Variant chr4-154584139-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000508.5(FGA):c.2586C>T(p.Pro862=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0054 in 1,269,898 control chromosomes in the GnomAD database, including 229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 111 hom., cov: 28)

Exomes 𝑓: 0.0030 ( 118 hom. )

Consequence

FGA
NM_000508.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.17

Variant links:

Genes affected

FGA (HGNC:3661): (fibrinogen alpha chain) This gene encodes the alpha subunit of the coagulation factor fibrinogen, which is a component of the blood clot. Following vascular injury, the encoded preproprotein is proteolytically processed by thrombin during the conversion of fibrinogen to fibrin. Mutations in this gene lead to several disorders, including dysfibrinogenemia, hypofibrinogenemia, afibrinogenemia and renal amyloidosis. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that undergoes proteolytic processing. [provided by RefSeq, Jan 2016]

FGA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-154584139-G-A is Benign according to our data. Variant chr4-154584139-G-A is described in ClinVar as [Benign]. Clinvar id is 256329.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGA	NM_000508.5 linkuse as main transcript	c.2586C>T	p.Pro862=	synonymous_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGA	ENST00000651975.2 linkuse as main transcript	c.2586C>T	p.Pro862=	synonymous_variant	6/6			P1	P02671-1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

3307

AN:

96046

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0148

Gnomad ASJ

AF:

0.00189

Gnomad EAS

AF:

0.000430

Gnomad SAS

AF:

0.000690

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0280

Gnomad NFE

AF:

0.000508

Gnomad OTH

AF:

0.0299

GnomAD3 exomes

AF:

0.00678

AC:

1476

AN:

217590

Hom.:

AF XY:

0.00515

AC XY:

609

AN XY:

118332

show subpopulations

Gnomad AFR exome

AF:

0.0933

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.00276

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000231

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000426

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00302

AC:

3544

AN:

1173796

Hom.:

118

Cov.:

AF XY:

0.00267

AC XY:

1550

AN XY:

579742

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.00614

Gnomad4 ASJ exome

AF:

0.00181

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000306

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000266

Gnomad4 OTH exome

AF:

0.00831

GnomAD4 genome

AF:

0.0345

AC:

3319

AN:

96102

Hom.:

111

Cov.:

AF XY:

0.0332

AC XY:

1558

AN XY:

46948

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0148

Gnomad4 ASJ

AF:

0.00189

Gnomad4 EAS

AF:

0.000430

Gnomad4 SAS

AF:

0.000347

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000509

Gnomad4 OTH

AF:

0.0295

Alfa

AF:

0.00736

Hom.:

Bravo

AF:

0.0258

Asia WGS

AF:

0.00578

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 24, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.028

DANN

Benign

0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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