Genetic Variant FCN1:c.272-68T>C (chr9-134914488-A-G) – 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.272-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,495,954 control chromosomes in the GnomAD database, including 291,277 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 0.63 ( 30130 hom., cov: 33)

Exomes 𝑓: 0.62 ( 261147 hom. )

Consequence

FCN1
NM_002003.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.23

Publications

4 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=-1.01).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5 link	c.272-68T>C		intron_variant	Intron 3 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.272-68T>C		intron_variant	Intron 3 of 8	1	NM_002003.5	ENSP00000360871.3		O00602

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95096

AN:

151194

Hom.:

30120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.689

Gnomad AMI

AF:

0.813

Gnomad AMR

AF:

0.491

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.482

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.654

Gnomad MID

AF:

0.624

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.589

GnomAD4 exome

AF:

0.621

AC:

834630

AN:

1344638

Hom.:

261147

AF XY:

0.625

AC XY:

421983

AN XY:

675678

show subpopulations

African (AFR)

AF:

0.702

AC:

21830

AN:

31086

American (AMR)

AF:

0.393

AC:

17437

AN:

44352

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

15731

AN:

25370

East Asian (EAS)

AF:

0.453

AC:

17724

AN:

39088

South Asian (SAS)

AF:

0.704

AC:

59124

AN:

83954

European-Finnish (FIN)

AF:

0.640

AC:

33881

AN:

52980

Middle Eastern (MID)

AF:

0.624

AC:

3462

AN:

5552

European-Non Finnish (NFE)

AF:

0.627

AC:

630658

AN:

1005812

Other (OTH)

AF:

0.616

AC:

34783

AN:

56444

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

16790

33580

50370

67160

83950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16160

32320

48480

64640

80800

<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:

0.629

AC:

95156

AN:

151316

Hom.:

30130

Cov.:

AF XY:

0.629

AC XY:

46489

AN XY:

73914

show subpopulations

African (AFR)

AF:

0.689

AC:

28416

AN:

41240

American (AMR)

AF:

0.491

AC:

7479

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2156

AN:

3460

East Asian (EAS)

AF:

0.481

AC:

2464

AN:

5122

South Asian (SAS)

AF:

0.692

AC:

3335

AN:

4816

European-Finnish (FIN)

AF:

0.654

AC:

6840

AN:

10462

Middle Eastern (MID)

AF:

0.635

AC:

183

AN:

288

European-Non Finnish (NFE)

AF:

0.625

AC:

42326

AN:

67698

Other (OTH)

AF:

0.587

AC:

1233

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1859

3718

5576

7435

9294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.635

Hom.:

3764

Bravo

AF:

0.614

Asia WGS

AF:

0.578

AC:

2011

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.46

(source)

DANN

Benign

0.42

PhyloP100

-1.2

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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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