4-154584139-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000508.5(FGA):c.2586C>T(p.Pro862Pro) 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

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

familial dysfibrinogenemia
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital afibrinogenemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital fibrinogen deficiency
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
familial visceral amyloidosis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
thrombophilia
Inheritance: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp
AFib amyloidosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial hypofibrinogenemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

FGA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FGA	NM_000508.5 link	c.2586C>T	p.Pro862Pro	synonymous_variant	Exon 6 of 6		NP_000499.1	P02671-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGA	ENST00000651975.2 link	c.2586C>T	p.Pro862Pro	synonymous_variant	Exon 6 of 6			ENSP00000498441.1		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

GnomAD2 exomes

AF:

0.00678

AC:

1476

AN:

217590

AF XY:

0.00515

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 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

African (AFR)

AF:

0.105

AC:

2593

AN:

24656

American (AMR)

AF:

0.00614

AC:

205

AN:

33380

Ashkenazi Jewish (ASJ)

AF:

0.00181

AC:

AN:

21554

East Asian (EAS)

AF:

0.00

AC:

AN:

25236

South Asian (SAS)

AF:

0.000306

AC:

AN:

58770

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40718

Middle Eastern (MID)

AF:

0.00930

AC:

AN:

4626

European-Non Finnish (NFE)

AF:

0.000266

AC:

244

AN:

916456

Other (OTH)

AF:

0.00831

AC:

402

AN:

48400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

161

323

484

646

807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0345

AC:

3319

AN:

96102

Hom.:

111

Cov.:

AF XY:

0.0332

AC XY:

1558

AN XY:

46948

show subpopulations

African (AFR)

AF:

0.128

AC:

3089

AN:

24116

American (AMR)

AF:

0.0148

AC:

153

AN:

10342

Ashkenazi Jewish (ASJ)

AF:

0.00189

AC:

AN:

2642

East Asian (EAS)

AF:

0.000430

AC:

AN:

2324

South Asian (SAS)

AF:

0.000347

AC:

AN:

2884

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6380

Middle Eastern (MID)

AF:

0.0294

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.000509

AC:

AN:

45224

Other (OTH)

AF:

0.0295

AC:

AN:

1388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

146

292

438

584

730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00814

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

Dec 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 24, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.028

(source)

DANN

Benign

0.59

PhyloP100

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

4-154584139-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over