9-134885525-G-C

Variant names:

• chr9-134885525-G-C
• rs56117058
• NM_004108.3:c.429+159G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004108.3(FCN2):​c.429+159G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,092 control chromosomes in the GnomAD database, including 1,979 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 (1979 hom., cov: 32)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0800
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.429+159G>C		intron	N/A	NP_004099.2
	FCN2	NM_015837.3		c.315+159G>C		intron	N/A	NP_056652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.429+159G>C		intron	N/A	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.315+159G>C		intron	N/A	ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21924 AN: 151974 Hom.: 1984 Cov.: 32

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.00310

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.144 AC: 21912 AN: 152092 Hom.: 1979 Cov.: 32 AF XY: 0.143 AC XY: 10658 AN XY: 74336

African (AFR) AF: 0.0666 AC: 2766 AN: 41518

American (AMR) AF: 0.122 AC: 1862 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3468

East Asian (EAS) AF: 0.00311 AC: 16 AN: 5148

South Asian (SAS) AF: 0.133 AC: 642 AN: 4830

European-Finnish (FIN) AF: 0.208 AC: 2199 AN: 10562

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.191 AC: 13006 AN: 67956

Other (OTH) AF: 0.144 AC: 304 AN: 2108

Alfa AF: 0.0838 Hom.: 111

Bravo AF: 0.133

Asia WGS AF: 0.0760 AC: 263 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.73
PhyloP100		-0.080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56117058; hg19: chr9-137777371;