Genetic Variant FCN1:p.Gln275Gln (chr9-134909954-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002003.5(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
NM_002003.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.41

Publications

28 publications found

Variant links:

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]

FCN1 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5 link	c.825A>G	p.Gln275Gln	synonymous_variant	Exon 9 of 9	ENST00000371806.4	NP_001994.2	O00602

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4 link	c.825A>G	p.Gln275Gln	synonymous_variant	Exon 9 of 9	1	NM_002003.5	ENSP00000360871.3		O00602

Frequencies

GnomAD3 genomes

AF:

0.699

AC:

106287

AN:

151982

Hom.:

38522

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.640

AC XY:

465480

AN XY:

727208

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

19097

38194

57291

76388

95485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.699

AC:

106380

AN:

152100

Hom.:

38568

Cov.:

AF XY:

0.697

AC XY:

51829

AN XY:

74336

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1542

3085

4627

6170

7712

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.58

(source)

DANN

Benign

0.44

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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9-134909954-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over