Genetic Variant NM_004108.3:c.214+80G>C (chr9-134882719-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_004108.3(FCN2):c.214+80G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 999,720 control chromosomes in the GnomAD database, including 11 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 0.0048 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 6 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.105

Publications

1 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=-0.91).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00483 (736/152304) while in subpopulation AFR AF = 0.0167 (692/41554). AF 95% confidence interval is 0.0156. There are 5 homozygotes in GnomAd4. There are 342 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3 link	c.214+80G>C	intron_variant	Intron 2 of 7	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 link	c.101-583G>C	intron_variant	Intron 1 of 6		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 link	c.181+80G>C	intron_variant	Intron 2 of 7		XP_011516694.1
FCN2	XM_006717015.5 link	c.68-583G>C	intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.214+80G>C		intron_variant	Intron 2 of 7	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 link	c.101-583G>C		intron_variant	Intron 1 of 6	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00484

AC:

736

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0167

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD4 exome

AF:

0.000662

AC:

561

AN:

847416

Hom.:

AF XY:

0.000565

AC XY:

249

AN XY:

440938

show subpopulations

African (AFR)

AF:

0.0196

AC:

418

AN:

21280

American (AMR)

AF:

0.00128

AC:

AN:

38422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19922

East Asian (EAS)

AF:

0.00

AC:

AN:

36474

South Asian (SAS)

AF:

0.0000296

AC:

AN:

67638

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46158

Middle Eastern (MID)

AF:

0.00199

AC:

AN:

4512

European-Non Finnish (NFE)

AF:

0.0000384

AC:

AN:

573208

Other (OTH)

AF:

0.00153

AC:

AN:

39802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00483

AC:

736

AN:

152304

Hom.:

Cov.:

AF XY:

0.00459

AC XY:

342

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0167

AC:

692

AN:

41554

American (AMR)

AF:

0.00176

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68012

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000978

Hom.:

Bravo

AF:

0.00580

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.64

(source)

DANN

Benign

0.34

PhyloP100

-0.10

Mutation Taster

=100/0

polymorphism

(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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NM_004108.3:c.214+80G>C

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