dbSNP rs12685659: FCN2:c.301+101A>T (chr9-134884873-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000291744.11(FCN2):c.301+101A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 1,068,764 control chromosomes in the GnomAD database, including 6,197 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 0.083 ( 652 hom., cov: 33)

Exomes 𝑓: 0.10 ( 5545 hom. )

Consequence

FCN2
ENST00000291744.11 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.345

Publications

6 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000291744.11. 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
	FCN2	NM_004108.3	MANE Select	c.301+101A>T		intron	N/A	NP_004099.2
	FCN2	NM_015837.3		c.187+101A>T		intron	N/A	NP_056652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.301+101A>T		intron	N/A	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.187+101A>T		intron	N/A	ENSP00000291741.5

Frequencies

GnomAD3 genomes

AF:

0.0832

AC:

12658

AN:

152190

Hom.:

652

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0214

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0357

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.110

Gnomad FIN

AF:

0.0945

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.0860

GnomAD4 exome

AF:

0.105

AC:

96045

AN:

916456

Hom.:

5545

AF XY:

0.105

AC XY:

49636

AN XY:

472482

show subpopulations

African (AFR)

AF:

0.0169

AC:

383

AN:

22676

American (AMR)

AF:

0.131

AC:

4766

AN:

36320

Ashkenazi Jewish (ASJ)

AF:

0.0396

AC:

882

AN:

22268

East Asian (EAS)

AF:

0.153

AC:

5249

AN:

34214

South Asian (SAS)

AF:

0.110

AC:

7818

AN:

70776

European-Finnish (FIN)

AF:

0.104

AC:

5040

AN:

48588

Middle Eastern (MID)

AF:

0.0463

AC:

219

AN:

4732

European-Non Finnish (NFE)

AF:

0.107

AC:

67716

AN:

634688

Other (OTH)

AF:

0.0941

AC:

3972

AN:

42194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

4976

9952

14928

19904

24880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1834

3668

5502

7336

9170

<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:

0.0832

AC:

12668

AN:

152308

Hom.:

652

Cov.:

AF XY:

0.0838

AC XY:

6242

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0213

AC:

886

AN:

41566

American (AMR)

AF:

0.103

AC:

1576

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0357

AC:

124

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

926

AN:

5184

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4824

European-Finnish (FIN)

AF:

0.0945

AC:

1003

AN:

10614

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.109

AC:

7410

AN:

68020

Other (OTH)

AF:

0.0880

AC:

186

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

608

1215

1823

2430

3038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<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:

0.0991

Hom.:

Bravo

AF:

0.0812

Asia WGS

AF:

0.135

AC:

470

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

6.6

(source)

DANN

Benign

0.47

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over