dbSNP rs3128624: FCN2:c.215-9A>G (chr9-134883293-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_004108.3(FCN2):c.215-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,595,166 control chromosomes in the GnomAD database, including 100,983 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 0.35 ( 9328 hom., cov: 32)

Exomes 𝑓: 0.35 ( 91655 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Splicing: ADA: 0.00001236

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

13 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:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.215-9A>G		intron	N/A	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.101-9A>G		intron	N/A	NP_056652.1	Q15485-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCN2	ENST00000291744.11	TSL:1 MANE Select	c.215-9A>G	intron	N/A	ENSP00000291744.6	Q15485-1
FCN2	ENST00000855732.1		c.215-9A>G	intron	N/A	ENSP00000525791.1
FCN2	ENST00000855735.1		c.215-9A>G	intron	N/A	ENSP00000525794.1

Frequencies

GnomAD3 genomes

AF:

0.348

AC:

52879

AN:

151868

Hom.:

9318

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.190

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.435

Gnomad SAS

AF:

0.435

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.343

Gnomad OTH

AF:

0.373

GnomAD2 exomes

AF:

0.361

AC:

90600

AN:

250944

AF XY:

0.368

show subpopulations

Gnomad AFR exome

AF:

0.335

Gnomad AMR exome

AF:

0.266

Gnomad ASJ exome

AF:

0.467

Gnomad EAS exome

AF:

0.444

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.351

Gnomad OTH exome

AF:

0.363

GnomAD4 exome

AF:

0.350

AC:

505688

AN:

1443180

Hom.:

91655

Cov.:

AF XY:

0.353

AC XY:

253724

AN XY:

718934

show subpopulations

African (AFR)

AF:

0.327

AC:

10818

AN:

33076

American (AMR)

AF:

0.275

AC:

12304

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

12144

AN:

25990

East Asian (EAS)

AF:

0.407

AC:

16110

AN:

39594

South Asian (SAS)

AF:

0.428

AC:

36727

AN:

85856

European-Finnish (FIN)

AF:

0.368

AC:

19605

AN:

53340

Middle Eastern (MID)

AF:

0.411

AC:

2357

AN:

5740

European-Non Finnish (NFE)

AF:

0.341

AC:

373552

AN:

1095146

Other (OTH)

AF:

0.369

AC:

22071

AN:

59742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.414

Heterozygous variant carriers

15923

31847

47770

63694

79617

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12012

24024

36036

48048

60060

<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:

0.348

AC:

52912

AN:

151986

Hom.:

9328

Cov.:

AF XY:

0.348

AC XY:

25887

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.333

AC:

13812

AN:

41462

American (AMR)

AF:

0.318

AC:

4862

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.465

AC:

1614

AN:

3470

East Asian (EAS)

AF:

0.435

AC:

2229

AN:

5130

South Asian (SAS)

AF:

0.436

AC:

2094

AN:

4806

European-Finnish (FIN)

AF:

0.372

AC:

3933

AN:

10578

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.343

AC:

23281

AN:

67944

Other (OTH)

AF:

0.378

AC:

797

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1781

3563

5344

7126

8907

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.351

Hom.:

12478

Bravo

AF:

0.344

Asia WGS

AF:

0.424

AC:

1473

AN:

3478

EpiCase

AF:

0.357

EpiControl

AF:

0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

9.0

(source)

DANN

Benign

0.47

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000012

dbscSNV1_RF

Benign

0.0040

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over