dbSNP rs12684512: FCN2:c.430-110G>A (chr9-134885658-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_004108.3(FCN2):c.430-110G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,470,876 control chromosomes in the GnomAD database, including 10,460 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 0.13 ( 1366 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9094 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.52

Publications

7 publications found

Variant links:

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is 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. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FCN2 links:

Genome browser will be placed here

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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3 link	c.430-110G>A	intron_variant	Intron 5 of 7	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 link	c.316-110G>A	intron_variant	Intron 4 of 6		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 link	c.397-110G>A	intron_variant	Intron 5 of 7		XP_011516694.1
FCN2	XM_006717015.5 link	c.283-110G>A	intron_variant	Intron 4 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.430-110G>A		intron_variant	Intron 5 of 7	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 link	c.316-110G>A		intron_variant	Intron 4 of 6	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19795

AN:

151860

Hom.:

1365

Cov.:

show subpopulations

Gnomad AFR

AF:

0.180

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0946

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.127

GnomAD4 exome

AF:

0.114

AC:

150420

AN:

1318898

Hom.:

9094

AF XY:

0.114

AC XY:

74828

AN XY:

658886

show subpopulations

African (AFR)

AF:

0.186

AC:

5720

AN:

30834

American (AMR)

AF:

0.144

AC:

6036

AN:

41848

Ashkenazi Jewish (ASJ)

AF:

0.0463

AC:

1061

AN:

22892

East Asian (EAS)

AF:

0.159

AC:

6114

AN:

38564

South Asian (SAS)

AF:

0.122

AC:

9474

AN:

77684

European-Finnish (FIN)

AF:

0.105

AC:

5039

AN:

47906

Middle Eastern (MID)

AF:

0.0697

AC:

293

AN:

4202

European-Non Finnish (NFE)

AF:

0.111

AC:

110566

AN:

999680

Other (OTH)

AF:

0.111

AC:

6117

AN:

55288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

6632

13264

19897

26529

33161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4022

8044

12066

16088

20110

<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:

0.130

AC:

19820

AN:

151978

Hom.:

1366

Cov.:

AF XY:

0.129

AC XY:

9600

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.180

AC:

7446

AN:

41420

American (AMR)

AF:

0.125

AC:

1915

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0418

AC:

145

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

919

AN:

5130

South Asian (SAS)

AF:

0.121

AC:

583

AN:

4818

European-Finnish (FIN)

AF:

0.0946

AC:

1002

AN:

10592

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7509

AN:

67934

Other (OTH)

AF:

0.129

AC:

271

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

839

1678

2517

3356

4195

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

220

440

660

880

1100

<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:

0.116

Hom.:

1146

Bravo

AF:

0.135

Asia WGS

AF:

0.154

AC:

539

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.6

(source)

DANN

Benign

0.72

PhyloP100

-1.5

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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