dbSNP rs7865453: FCN2:c.68-1768A>C (chr9-134880758-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The XM_011518392.4(FCN2):c.68-1768A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 1,296,572 control chromosomes in the GnomAD database, including 8,725 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 0.14 ( 1638 hom., cov: 33)

Exomes 𝑓: 0.11 ( 7087 hom. )

Consequence

FCN2
XM_011518392.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0930

Publications

23 publications found

Variant links:

COSMIC-nc: COSV52477130

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:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FCN2	XM_011518392.4 link	c.68-1768A>C	intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5 link	c.68-2544A>C	intron_variant	Intron 1 of 6		XP_006717078.1
FCN2	NM_004108.3 link	c.-64A>C	upstream_gene_variant		ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 link	c.-64A>C	upstream_gene_variant			NP_056652.1	Q15485-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.-64A>C		upstream_gene_variant		1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 link	c.-64A>C		upstream_gene_variant		5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.136

AC:

20728

AN:

152100

Hom.:

1629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.0121

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0427

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.115

Gnomad FIN

AF:

0.0900

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.101

Gnomad OTH

AF:

0.134

GnomAD4 exome

AF:

0.106

AC:

121503

AN:

1144354

Hom.:

7087

AF XY:

0.106

AC XY:

61319

AN XY:

581090

show subpopulations

African (AFR)

AF:

0.224

AC:

6048

AN:

27054

American (AMR)

AF:

0.144

AC:

5887

AN:

40850

Ashkenazi Jewish (ASJ)

AF:

0.0489

AC:

1158

AN:

23662

East Asian (EAS)

AF:

0.155

AC:

5834

AN:

37758

South Asian (SAS)

AF:

0.114

AC:

8796

AN:

77228

European-Finnish (FIN)

AF:

0.0999

AC:

5103

AN:

51072

Middle Eastern (MID)

AF:

0.0688

AC:

356

AN:

5176

European-Non Finnish (NFE)

AF:

0.0998

AC:

83023

AN:

831768

Other (OTH)

AF:

0.106

AC:

5298

AN:

49786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

5634

11267

16901

22534

28168

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2794

5588

8382

11176

13970

<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:

0.137

AC:

20782

AN:

152218

Hom.:

1638

Cov.:

AF XY:

0.134

AC XY:

10008

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.220

AC:

9136

AN:

41506

American (AMR)

AF:

0.123

AC:

1887

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0427

AC:

148

AN:

3468

East Asian (EAS)

AF:

0.180

AC:

929

AN:

5174

South Asian (SAS)

AF:

0.116

AC:

559

AN:

4828

European-Finnish (FIN)

AF:

0.0900

AC:

955

AN:

10616

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.101

AC:

6859

AN:

68020

Other (OTH)

AF:

0.135

AC:

284

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

911

1822

2732

3643

4554

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.0749

Hom.:

Bravo

AF:

0.145

Asia WGS

AF:

0.150

AC:

527

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

3.2

(source)

DANN

Benign

0.52

PhyloP100

-0.093

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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