rs148317511

Positions:

• chr4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTC

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000508.5(FGA):​c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,366,810 control chromosomes in the GnomAD database, including 46,544 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6505 hom., cov: 29)
  • Exomes 𝑓: 0.23 (40039 hom.)
• Consequence: FGA NM_000508.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTC is Benign according to our data. Variant chr4-154584089-A-AGAAGACAGAGTGCTCCCATTCCCACTTC is described in ClinVar as [Benign]. Clinvar id is 256327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGA	NM_000508.5	c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTC		3_prime_UTR_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGA	ENST00000651975.2	c.*34_*35insGAAGTGGGAATGGGAGCACTCTGTCTTC		3_prime_UTR_variant	6/6			P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43484 AN: 150588 Hom.: 6494 Cov.: 29

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.231 AC: 280324 AN: 1216106 Hom.: 40039 Cov.: 24 AF XY: 0.235 AC XY: 145086 AN XY: 616588

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.463

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.289 AC: 43527 AN: 150704 Hom.: 6505 Cov.: 29 AF XY: 0.289 AC XY: 21284 AN XY: 73542

Gnomad4 AFR AF: 0.357

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.254

Alfa AF: 0.211 Hom.: 593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs148317511; hg19: chr4-155505241;