rs1071583

Variant names:

• chr9-134909954-T-C
• rs1071583
• NM_002003.5:c.825A>G

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000371806.4(FCN1):​c.825A>G​(p.Gln275Gln) 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 ENST00000371806.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.41
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000371806.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	NM_002003.5	MANE Select	c.825A>G	p.Gln275Gln	synonymous	Exon 9 of 9	NP_001994.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	ENST00000371806.4	TSL:1 MANE Select	c.825A>G	p.Gln275Gln	synonymous	Exon 9 of 9	ENSP00000360871.3

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

GnomAD2 exomes AF: 0.625 AC: 157129 AN: 251484 AF XY: 0.633

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 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

African (AFR) AF: 0.915 AC: 30630 AN: 33478

American (AMR) AF: 0.416 AC: 18621 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 16031 AN: 26134

East Asian (EAS) AF: 0.455 AC: 18081 AN: 39700

South Asian (SAS) AF: 0.719 AC: 61998 AN: 86256

European-Finnish (FIN) AF: 0.658 AC: 35125 AN: 53418

Middle Eastern (MID) AF: 0.666 AC: 3844 AN: 5768

European-Non Finnish (NFE) AF: 0.637 AC: 708073 AN: 1111918

Other (OTH) AF: 0.643 AC: 38824 AN: 60394

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

African (AFR) AF: 0.898 AC: 37310 AN: 41526

American (AMR) AF: 0.529 AC: 8082 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.617 AC: 2140 AN: 3470

East Asian (EAS) AF: 0.488 AC: 2514 AN: 5148

South Asian (SAS) AF: 0.707 AC: 3406 AN: 4820

European-Finnish (FIN) AF: 0.674 AC: 7128 AN: 10568

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.640 AC: 43478 AN: 67968

Other (OTH) AF: 0.650 AC: 1371 AN: 2108

Alfa AF: 0.651 Hom.: 52275

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.58
DANN	Benign	0.44
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1071583; hg19: chr9-137801800; COSMIC: COSV65662195;