Genetic Variant NM_004108.3:c.695-127T>G (chr9-134887041-T-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.695-127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,079,162 control chromosomes in the GnomAD database, including 8,106 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 ( 1472 hom., cov: 33)

Exomes 𝑓: 0.12 ( 6634 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.62

Publications

9 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3 link	c.695-127T>G	intron_variant	Intron 7 of 7	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 link	c.581-127T>G	intron_variant	Intron 6 of 6		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 link	c.662-127T>G	intron_variant	Intron 7 of 7		XP_011516694.1
FCN2	XM_006717015.5 link	c.548-127T>G	intron_variant	Intron 6 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.695-127T>G		intron_variant	Intron 7 of 7	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 link	c.581-127T>G		intron_variant	Intron 6 of 6	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20565

AN:

152120

Hom.:

1472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.0418

Gnomad EAS

AF:

0.180

Gnomad SAS

AF:

0.122

Gnomad FIN

AF:

0.0947

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.130

GnomAD4 exome

AF:

0.115

AC:

106680

AN:

926924

Hom.:

6634

AF XY:

0.115

AC XY:

55265

AN XY:

482612

show subpopulations

African (AFR)

AF:

0.196

AC:

4521

AN:

23014

American (AMR)

AF:

0.145

AC:

6282

AN:

43202

Ashkenazi Jewish (ASJ)

AF:

0.0467

AC:

1058

AN:

22638

East Asian (EAS)

AF:

0.158

AC:

5877

AN:

37242

South Asian (SAS)

AF:

0.123

AC:

9177

AN:

74406

European-Finnish (FIN)

AF:

0.104

AC:

4948

AN:

47490

Middle Eastern (MID)

AF:

0.0737

AC:

229

AN:

3106

European-Non Finnish (NFE)

AF:

0.110

AC:

69846

AN:

633126

Other (OTH)

AF:

0.111

AC:

4742

AN:

42700

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

5105

10210

15315

20420

25525

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1896

3792

5688

7584

9480

<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:

0.135

AC:

20589

AN:

152238

Hom.:

1472

Cov.:

AF XY:

0.133

AC XY:

9928

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.196

AC:

8120

AN:

41528

American (AMR)

AF:

0.126

AC:

1924

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0418

AC:

145

AN:

3468

East Asian (EAS)

AF:

0.181

AC:

935

AN:

5166

South Asian (SAS)

AF:

0.122

AC:

588

AN:

4826

European-Finnish (FIN)

AF:

0.0947

AC:

1005

AN:

10612

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7565

AN:

68020

Other (OTH)

AF:

0.131

AC:

277

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

943

1886

2828

3771

4714

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0860

Hom.:

218

Bravo

AF:

0.141

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

-0.88

CADD

Benign

2.9

(source)

DANN

Benign

0.78

PhyloP100

-2.6

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

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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