4-154583796-G-A

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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=-0.81).
• 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_single_submitter, 1 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	UniProt
FGA	NM_000508.5	c.*328C>T		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGA	ENST00000651975.2	c.*328C>T		3_prime_UTR_variant	6/6			P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26726 AN: 151962 Hom.: 2664 Cov.: 32

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.: 0 AF XY: 0.171 AC XY: 10355 AN XY: 60382

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.: 32 AF XY: 0.181 AC XY: 13471 AN XY: 74326

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	10
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

Other links and lift over

dbSNP: rs2070022; hg19: chr4-155504948; COSMIC: COSV57400052; COSMIC: COSV57400052;