rs1071583

Positions:

• chr9-134909954-T-C
• chr9-134909954-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002003.5(FCN1):​c.825A>G​(p.Gln275=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 1,613,890 control chromosomes in the GnomAD database, including 339,132 homozygotes. 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: 𝑓 0.70 (38568 hom., cov: 32)
  • Exomes 𝑓: 0.64 (300564 hom.)
• Consequence: FCN1 NM_002003.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41

Genes affected

FCN1 (HGNC:3623): (ficolin 1) The ficolin family of proteins are characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=-3.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN1	NM_002003.5	c.825A>G	p.Gln275=	synonymous_variant	9/9	ENST00000371806.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN1	ENST00000371806.4	c.825A>G	p.Gln275=	synonymous_variant	9/9	1	NM_002003.5	P1

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106287 AN: 151982 Hom.: 38522 Cov.: 32

Gnomad AFR AF: 0.898

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.617

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.640

Gnomad OTH AF: 0.653

GnomAD3 exomes AF: 0.625 AC: 157129 AN: 251484 Hom.: 51247 AF XY: 0.633 AC XY: 86036 AN XY: 135916

Gnomad AFR exome AF: 0.912

Gnomad AMR exome AF: 0.403

Gnomad ASJ exome AF: 0.614

Gnomad EAS exome AF: 0.485

Gnomad SAS exome AF: 0.717

Gnomad FIN exome AF: 0.666

Gnomad NFE exome AF: 0.643

Gnomad OTH exome AF: 0.616

GnomAD4 exome AF: 0.637 AC: 931227 AN: 1461790 Hom.: 300564 Cov.: 48 AF XY: 0.640 AC XY: 465480 AN XY: 727208

Gnomad4 AFR exome AF: 0.915

Gnomad4 AMR exome AF: 0.416

Gnomad4 ASJ exome AF: 0.613

Gnomad4 EAS exome AF: 0.455

Gnomad4 SAS exome AF: 0.719

Gnomad4 FIN exome AF: 0.658

Gnomad4 NFE exome AF: 0.637

Gnomad4 OTH exome AF: 0.643

GnomAD4 genome AF: 0.699 AC: 106380 AN: 152100 Hom.: 38568 Cov.: 32 AF XY: 0.697 AC XY: 51829 AN XY: 74336

Gnomad4 AFR AF: 0.898

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.617

Gnomad4 EAS AF: 0.488

Gnomad4 SAS AF: 0.707

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.640

Gnomad4 OTH AF: 0.650

Alfa AF: 0.647 Hom.: 41995

Bravo AF: 0.692

Asia WGS AF: 0.603 AC: 2097 AN: 3478

EpiCase AF: 0.629

EpiControl AF: 0.629

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1071583; hg19: chr9-137801800; COSMIC: COSV65662195;