Genetic Variant NM_004108.3:c.-4A>G (chr9-134880818-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.-4A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,610,128 control chromosomes in the GnomAD database, including 55,295 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 0.24 ( 4776 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50519 hom. )

Consequence

FCN2
NM_004108.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0590

Publications

54 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=-0.93).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 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.-4A>G		5_prime_UTR	Exon 1 of 8	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.-4A>G		5_prime_UTR	Exon 1 of 7	NP_056652.1	Q15485-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCN2	ENST00000291744.11	TSL:1 MANE Select	c.-4A>G	5_prime_UTR	Exon 1 of 8	ENSP00000291744.6	Q15485-1
FCN2	ENST00000855732.1		c.-4A>G	5_prime_UTR	Exon 1 of 8	ENSP00000525791.1
FCN2	ENST00000855735.1		c.-4A>G	5_prime_UTR	Exon 1 of 8	ENSP00000525794.1

Frequencies

GnomAD3 genomes

AF:

0.244

AC:

37076

AN:

152028

Hom.:

4783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.578

Gnomad AMR

AF:

0.219

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.0659

Gnomad SAS

AF:

0.208

Gnomad FIN

AF:

0.285

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.232

GnomAD2 exomes

AF:

0.230

AC:

56907

AN:

247884

AF XY:

0.231

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.183

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.0555

Gnomad FIN exome

AF:

0.277

Gnomad NFE exome

AF:

0.274

Gnomad OTH exome

AF:

0.240

GnomAD4 exome

AF:

0.259

AC:

378201

AN:

1457982

Hom.:

50519

Cov.:

AF XY:

0.259

AC XY:

187989

AN XY:

725332

show subpopulations

African (AFR)

AF:

0.196

AC:

6542

AN:

33414

American (AMR)

AF:

0.189

AC:

8438

AN:

44628

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

6220

AN:

26064

East Asian (EAS)

AF:

0.0606

AC:

2404

AN:

39684

South Asian (SAS)

AF:

0.210

AC:

18037

AN:

86034

European-Finnish (FIN)

AF:

0.274

AC:

14524

AN:

53044

Middle Eastern (MID)

AF:

0.257

AC:

1482

AN:

5762

European-Non Finnish (NFE)

AF:

0.276

AC:

305610

AN:

1109098

Other (OTH)

AF:

0.248

AC:

14944

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

13678

27356

41033

54711

68389

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9958

19916

29874

39832

49790

<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:

0.244

AC:

37069

AN:

152146

Hom.:

4776

Cov.:

AF XY:

0.242

AC XY:

17973

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.203

AC:

8445

AN:

41522

American (AMR)

AF:

0.219

AC:

3348

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3468

East Asian (EAS)

AF:

0.0655

AC:

339

AN:

5174

South Asian (SAS)

AF:

0.206

AC:

995

AN:

4826

European-Finnish (FIN)

AF:

0.285

AC:

3021

AN:

10588

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18951

AN:

67974

Other (OTH)

AF:

0.229

AC:

485

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1462

2925

4387

5850

7312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

382

764

1146

1528

1910

<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:

0.257

Hom.:

4948

Bravo

AF:

0.235

Asia WGS

AF:

0.152

AC:

526

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.059

PromoterAI

-0.017

Neutral

(source)

Mutation Taster

=300/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over