rs2070017

Variant names:

Variant summary

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

The NM_021871.4(FGA):c.181-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00973 in 741,652 control chromosomes in the GnomAD database, including 384 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 262 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 122 hom. )

Consequence

FGA
NM_021871.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.451

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:

ENSG00000306549 (HGNC:):

ENSG00000306549 links:

Genome browser will be placed here

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=-0.83).

BP6

Variant 4-154589124-C-T is Benign according to our data. Variant chr4-154589124-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGA	NM_021871.4 link	c.181-148G>A		intron_variant	Intron 2 of 4	ENST00000403106.8	NP_068657.1	P02671-2
FGA	NM_000508.5 link	c.181-148G>A		intron_variant	Intron 2 of 5		NP_000499.1	P02671-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FGA	ENST00000403106.8 link	c.181-148G>A	intron_variant	Intron 2 of 4	1	NM_021871.4	ENSP00000385981.3	P02671-2
FGA	ENST00000651975.2 link	c.181-148G>A	intron_variant	Intron 2 of 5			ENSP00000498441.1	P02671-1
ENSG00000306549	ENST00000819308.1 link	n.137+2360C>T	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0316

AC:

4805

AN:

151986

Hom.:

259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.00405

AC:

2389

AN:

589548

Hom.:

122

AF XY:

0.00364

AC XY:

1138

AN XY:

312456

show subpopulations

African (AFR)

AF:

0.108

AC:

1594

AN:

14814

American (AMR)

AF:

0.00704

AC:

174

AN:

24700

Ashkenazi Jewish (ASJ)

AF:

0.00788

AC:

134

AN:

17014

East Asian (EAS)

AF:

0.00

AC:

AN:

32110

South Asian (SAS)

AF:

0.000280

AC:

AN:

53638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45428

Middle Eastern (MID)

AF:

0.00682

AC:

AN:

2346

European-Non Finnish (NFE)

AF:

0.000412

AC:

152

AN:

368662

Other (OTH)

AF:

0.00986

AC:

304

AN:

30836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.0317

AC:

4828

AN:

152104

Hom.:

262

Cov.:

AF XY:

0.0302

AC XY:

2244

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.109

AC:

4531

AN:

41462

American (AMR)

AF:

0.0108

AC:

165

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00749

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.000416

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000544

AC:

AN:

68014

Other (OTH)

AF:

0.0298

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

213

427

640

854

1067

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0185

Hom.:

Bravo

AF:

0.0360

Asia WGS

AF:

0.00837

AC:

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 12, 2021

GeneDx

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

-0.83

CADD

Benign

1.8

(source)

DANN

Benign

0.60

PhyloP100

-0.45

Mutation Taster

=100/0

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

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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