Variant 4-154583796-G-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 NM_000508.5(FGA):c.*328C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 267,466 control chromosomes in the GnomAD database, including 4,668 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2673 hom., cov: 32)

Exomes 𝑓: 0.17 ( 1995 hom. )

Consequence

FGA
NM_000508.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.28

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-154583796-G-A is Benign according to our data. Variant chr4-154583796-G-A is described in ClinVar as [Benign]. Clinvar id is 1252841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGA	NM_000508.5 linkuse as main transcript	c.*328C>T		3_prime_UTR_variant	6/6		NP_000499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGA	ENST00000651975.2 linkuse as main transcript	c.*328C>T		3_prime_UTR_variant	6/6			ENSP00000498441	P1	P02671-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26726

AN:

151962

Hom.:

2664

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.213

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.114

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.134

Gnomad NFE

AF:

0.172

Gnomad OTH

AF:

0.182

GnomAD4 exome

AF:

0.173

AC:

19919

AN:

115388

Hom.:

1995

Cov.:

AF XY:

0.171

AC XY:

10355

AN XY:

60382

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.312

Gnomad4 ASJ exome

AF:

0.138

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.181

Gnomad4 FIN exome

AF:

0.210

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.174

GnomAD4 genome

AF:

0.176

AC:

26746

AN:

152078

Hom.:

2673

Cov.:

AF XY:

0.181

AC XY:

13471

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.303

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.113

Gnomad4 SAS

AF:

0.224

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.172

Gnomad4 OTH

AF:

0.188

Alfa

AF:

0.177

Hom.:

3469

Bravo

AF:

0.177

Asia WGS

AF:

0.182

AC:

632

AN:

3474

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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.67

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