chr4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTCGAAGACAGAGTGCTCCCATTCCCACTTC

Variant names:

• chr4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTCGAAGACAGAGTGCTCCCATTCCCACTTC
• NM_000508.5:c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC

Variant summary

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

The NM_000508.5(FGA):​c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 1,218,628 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: FGA NM_000508.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894

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_000508.5	c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC		3_prime_UTR_variant	Exon 6 of 6		NP_000499.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGA	ENST00000651975	c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC		3_prime_UTR_variant	Exon 6 of 6			ENSP00000498441.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000164 AC: 2 AN: 1218628 Hom.: 0 Cov.: 24 AF XY: 0.00000162 AC XY: 1 AN XY: 617794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000522

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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: chr4-155505241;