rs2070025

Variant names:

• chr4-154590672-T-A
• NM_021871.4:c.16A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-154590672-T-A
• chr4-154590672-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021871.4(FGA):​c.16A>T​(p.Ile6Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,405,528 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FGA NM_021871.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGA	NM_021871.4	c.16A>T	p.Ile6Phe	missense_variant	Exon 1 of 5	ENST00000403106.8	NP_068657.1
FGA	NM_000508.5	c.16A>T	p.Ile6Phe	missense_variant	Exon 1 of 6		NP_000499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGA	ENST00000403106.8	c.16A>T	p.Ile6Phe	missense_variant	Exon 1 of 5	1	NM_021871.4	ENSP00000385981.3
FGA	ENST00000651975.2	c.16A>T	p.Ile6Phe	missense_variant	Exon 1 of 6			ENSP00000498441.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1405528 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 693738

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.24e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.081	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	19
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.44	T;.;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.66	T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.3	M;M;.
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.7	N;N;.
REVEL	Benign	0.074
Sift	Uncertain	0.018	D;D;.
Sift4G	Uncertain	0.018	D;D;D
Polyphen		0.93	P;D;.
Vest4		0.13
MutPred		0.29		Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP		0.79
MPC		0.15
ClinPred		0.75	D
GERP RS		0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.078
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.45		Position offset: 2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-155511824;