Genetic Variant FCN1:c.468+32C>G (chr9-134912984-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002003.5(FCN1):c.468+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,596,904 control chromosomes in the GnomAD database, including 323,083 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 0.68 ( 36368 hom., cov: 33)

Exomes 𝑓: 0.63 ( 286715 hom. )

Consequence

FCN1
NM_002003.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.504

Publications

6 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5 link	c.468+32C>G		intron_variant	Intron 6 of 8	ENST00000371806.4	NP_001994.2	O00602

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4 link	c.468+32C>G		intron_variant	Intron 6 of 8	1	NM_002003.5	ENSP00000360871.3		O00602

Frequencies

GnomAD3 genomes

AF:

0.681

AC:

103459

AN:

151994

Hom.:

36334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.859

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.486

Gnomad SAS

AF:

0.703

Gnomad FIN

AF:

0.657

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.629

Gnomad OTH

AF:

0.629

GnomAD2 exomes

AF:

0.615

AC:

137646

AN:

223858

AF XY:

0.624

show subpopulations

Gnomad AFR exome

AF:

0.873

Gnomad AMR exome

AF:

0.398

Gnomad ASJ exome

AF:

0.627

Gnomad EAS exome

AF:

0.483

Gnomad FIN exome

AF:

0.650

Gnomad NFE exome

AF:

0.635

Gnomad OTH exome

AF:

0.607

GnomAD4 exome

AF:

0.626

AC:

904923

AN:

1444792

Hom.:

286715

Cov.:

AF XY:

0.630

AC XY:

451634

AN XY:

717276

show subpopulations

African (AFR)

AF:

0.875

AC:

29098

AN:

33238

American (AMR)

AF:

0.411

AC:

17242

AN:

41982

Ashkenazi Jewish (ASJ)

AF:

0.624

AC:

16082

AN:

25774

East Asian (EAS)

AF:

0.451

AC:

17650

AN:

39108

South Asian (SAS)

AF:

0.714

AC:

60316

AN:

84434

European-Finnish (FIN)

AF:

0.640

AC:

32990

AN:

51532

Middle Eastern (MID)

AF:

0.647

AC:

3434

AN:

5308

European-Non Finnish (NFE)

AF:

0.626

AC:

690520

AN:

1103718

Other (OTH)

AF:

0.630

AC:

37591

AN:

59698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

17417

34835

52252

69670

87087

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18492

36984

55476

73968

92460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.681

AC:

103541

AN:

152112

Hom.:

36368

Cov.:

AF XY:

0.679

AC XY:

50510

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.859

AC:

35668

AN:

41528

American (AMR)

AF:

0.515

AC:

7863

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

2177

AN:

3466

East Asian (EAS)

AF:

0.485

AC:

2498

AN:

5146

South Asian (SAS)

AF:

0.702

AC:

3385

AN:

4822

European-Finnish (FIN)

AF:

0.657

AC:

6959

AN:

10588

Middle Eastern (MID)

AF:

0.667

AC:

196

AN:

294

European-Non Finnish (NFE)

AF:

0.629

AC:

42725

AN:

67964

Other (OTH)

AF:

0.626

AC:

1325

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1619

3238

4857

6476

8095

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.586

Hom.:

3286

Bravo

AF:

0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.4

(source)

DANN

Benign

0.76

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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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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