rs2070018

chr4-154587475-G-Achr4-154587475-G-Cchr4-154587475-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021871.4(FGA):c.510+37C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.876 in 1,605,114 control chromosomes in the GnomAD database, including 615,912 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.88 (58579 hom., cov: 30)
  • Exomes 𝑓: 0.88 (557333 hom.)
• Consequence: FGA NM_021871.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.169

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 4-154587475-G-A is Benign according to our data. Variant chr4-154587475-G-A is described in ClinVar as [Benign]. Clinvar id is 1268821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGA	NM_021871.4	c.510+37C>T		intron_variant		ENST00000403106.8
FGA	NM_000508.5	c.510+37C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGA	ENST00000403106.8	c.510+37C>T		intron_variant		1	NM_021871.4
FGA	ENST00000651975.2	c.510+37C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133348 AN: 151900 Hom.: 58534 Cov.: 30

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.885

Gnomad AMR AF: 0.875

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.885

GnomAD3 exomes AF: 0.873 AC: 219178 AN: 251038 Hom.: 95848 AF XY: 0.873 AC XY: 118490 AN XY: 135712

Gnomad AFR exome AF: 0.894

Gnomad AMR exome AF: 0.860

Gnomad ASJ exome AF: 0.796

Gnomad EAS exome AF: 0.949

Gnomad SAS exome AF: 0.860

Gnomad FIN exome AF: 0.849

Gnomad NFE exome AF: 0.877

Gnomad OTH exome AF: 0.870

GnomAD4 exome AF: 0.875 AC: 1272061 AN: 1453096 Hom.: 557333 Cov.: 28 AF XY: 0.875 AC XY: 633212 AN XY: 723490

Gnomad4 AFR exome AF: 0.898

Gnomad4 AMR exome AF: 0.862

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.965

Gnomad4 SAS exome AF: 0.858

Gnomad4 FIN exome AF: 0.849

Gnomad4 NFE exome AF: 0.877

Gnomad4 OTH exome AF: 0.870

GnomAD4 genome AF: 0.878 AC: 133450 AN: 152018 Hom.: 58579 Cov.: 30 AF XY: 0.877 AC XY: 65139 AN XY: 74296

Gnomad4 AFR AF: 0.895

Gnomad4 AMR AF: 0.875

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.884

Alfa AF: 0.870 Hom.: 50530

Bravo AF: 0.882

Asia WGS AF: 0.885 AC: 3078 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.88
Cadd	Benign	0.32
Dann	Benign	0.65

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

Other links and lift over

dbSNP: rs2070018; hg19: chr4-155508627;