rs2070011

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The ENST00000951262.1(FGA):c.-58A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,283,734 control chromosomes in the GnomAD database, including 251,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32380 hom., cov: 33)

Exomes 𝑓: 0.62 ( 219041 hom. )

Consequence

FGA
ENST00000951262.1 5_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.704

Publications

45 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital afibrinogenemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
congenital fibrinogen deficiency
Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
familial visceral amyloidosis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
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:

ENSG00000306549 (HGNC:):

ENSG00000306549 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000951262.1, 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=-0.82).

BP6

Variant 4-154590745-T-C is Benign according to our data. Variant chr4-154590745-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 347824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000951262.1. 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
	FGA	NM_021871.4	MANE Select	c.-58A>G		upstream_gene	N/A	NP_068657.1	P02671-2
	FGA	NM_000508.5		c.-58A>G		upstream_gene	N/A	NP_000499.1	P02671-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FGA	ENST00000951262.1		c.-58A>G	5_prime_UTR	Exon 1 of 4	ENSP00000621321.1
ENSG00000306549	ENST00000819308.1		n.138-2183T>C	intron	N/A
FGA	ENST00000403106.8	TSL:1 MANE Select	c.-58A>G	upstream_gene	N/A	ENSP00000385981.3	P02671-2

Frequencies

GnomAD3 genomes

AF:

0.648

AC:

98541

AN:

152022

Hom.:

32342

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.649

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.501

Gnomad SAS

AF:

0.556

Gnomad FIN

AF:

0.540

Gnomad MID

AF:

0.703

Gnomad NFE

AF:

0.621

Gnomad OTH

AF:

0.674

GnomAD4 exome

AF:

0.620

AC:

702012

AN:

1131594

Hom.:

219041

Cov.:

AF XY:

0.617

AC XY:

351984

AN XY:

570406

show subpopulations

African (AFR)

AF:

0.752

AC:

19761

AN:

26280

American (AMR)

AF:

0.634

AC:

22425

AN:

35368

Ashkenazi Jewish (ASJ)

AF:

0.677

AC:

15932

AN:

23540

East Asian (EAS)

AF:

0.499

AC:

17198

AN:

34432

South Asian (SAS)

AF:

0.533

AC:

39313

AN:

73794

European-Finnish (FIN)

AF:

0.532

AC:

26089

AN:

49054

Middle Eastern (MID)

AF:

0.699

AC:

3639

AN:

5208

European-Non Finnish (NFE)

AF:

0.630

AC:

526182

AN:

834840

Other (OTH)

AF:

0.641

AC:

31473

AN:

49078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

14421

28841

43262

57682

72103

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12810

25620

38430

51240

64050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.648

AC:

98635

AN:

152140

Hom.:

32380

Cov.:

AF XY:

0.643

AC XY:

47807

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.745

AC:

30960

AN:

41532

American (AMR)

AF:

0.650

AC:

9927

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.686

AC:

2379

AN:

3470

East Asian (EAS)

AF:

0.501

AC:

2585

AN:

5162

South Asian (SAS)

AF:

0.554

AC:

2673

AN:

4822

European-Finnish (FIN)

AF:

0.540

AC:

5721

AN:

10588

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.621

AC:

42184

AN:

67964

Other (OTH)

AF:

0.674

AC:

1424

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1790

3579

5369

7158

8948

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<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:

0.633

Hom.:

114135

Bravo

AF:

0.660

Asia WGS

AF:

0.580

AC:

2019

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital afibrinogenemia (1)

Familial visceral amyloidosis, Ostertag type (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

(source)

DANN

Benign

0.63

PhyloP100

-0.70

PromoterAI

-0.0038

Neutral

(source)

Mutation Taster

=114/186

disease causing (long InDel)

(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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over