rs2070016

Positions:

• chr4-154589162-A-G

Variant summary

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

The ENST00000403106.8(FGA):​c.181-186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,108 control chromosomes in the GnomAD database, including 1,343 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.12 (1343 hom., cov: 32)
• Consequence: FGA ENST00000403106.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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=-0.87).
• BP6: Variant 4-154589162-A-G is Benign according to our data. Variant chr4-154589162-A-G is described in ClinVar as [Benign]. Clinvar id is 1279619.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGA	NM_021871.4	c.181-186T>C		intron_variant		ENST00000403106.8	NP_068657.1
FGA	NM_000508.5	c.181-186T>C		intron_variant			NP_000499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGA	ENST00000403106.8	c.181-186T>C		intron_variant		1	NM_021871.4	ENSP00000385981
FGA	ENST00000651975.2	c.181-186T>C		intron_variant				ENSP00000498441	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18654 AN: 151990 Hom.: 1341 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.141

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18658 AN: 152108 Hom.: 1343 Cov.: 32 AF XY: 0.122 AC XY: 9051 AN XY: 74374

Gnomad4 AFR AF: 0.0540

Gnomad4 AMR AF: 0.110

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.151

Gnomad4 OTH AF: 0.139

Alfa AF: 0.152 Hom.: 3778

Bravo AF: 0.120

Asia WGS AF: 0.151 AC: 526 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	-0.87
CADD	Benign	0.40
DANN	Benign	0.37

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: rs2070016; hg19: chr4-155510314;