NM_000508.5:c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC

Variant names:

• chr4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTCGAAGACAGAGTGCTCCCATTCCCACTTC
• rs148317511
• NM_000508.5:c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTCGAAGTGGGAATGGGAGCACTCTGTCTTC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Publications: 0 publications found

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]

FGA Gene-Disease associations (from GenCC):

• familial dysfibrinogenemia

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital afibrinogenemia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital fibrinogen deficiency

  Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
• familial visceral amyloidosis

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• thrombophilia

  Inheritance: AR, AD Classification: STRONG Submitted by: Genomics England PanelApp
• AFib amyloidosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial hypofibrinogenemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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	ENST00000651975.2	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

African (AFR) AF: 0.00 AC: 0 AN: 27682

American (AMR) AF: 0.00 AC: 0 AN: 44422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24838

East Asian (EAS) AF: 0.0000522 AC: 2 AN: 38282

South Asian (SAS) AF: 0.00 AC: 0 AN: 80882

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53262

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4220

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 892746

Other (OTH) AF: 0.00 AC: 0 AN: 52294

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs148317511; hg19: chr4-155505241;