NM_004108.3:c.269-532G>A

Variant names:

• chr9-134884208-G-A
• rs7041446
• NM_004108.3:c.269-532G>A

Variant summary

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

The NM_004108.3(FCN2):​c.269-532G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,924 control chromosomes in the GnomAD database, including 17,215 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 0.47 (17215 hom., cov: 31)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.354
• Publications: 0 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 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.269-532G>A		intron	N/A	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.155-532G>A		intron	N/A	NP_056652.1	Q15485-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.269-532G>A		intron	N/A	ENSP00000291744.6	Q15485-1
	FCN2	ENST00000855732.1		c.390-532G>A		intron	N/A	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.332-532G>A		intron	N/A	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71978 AN: 151806 Hom.: 17198 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.213

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.474 AC: 72033 AN: 151924 Hom.: 17215 Cov.: 31 AF XY: 0.473 AC XY: 35100 AN XY: 74258

African (AFR) AF: 0.501 AC: 20743 AN: 41390

American (AMR) AF: 0.438 AC: 6685 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1678 AN: 3466

East Asian (EAS) AF: 0.610 AC: 3145 AN: 5154

South Asian (SAS) AF: 0.558 AC: 2680 AN: 4806

European-Finnish (FIN) AF: 0.466 AC: 4927 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.453 AC: 30799 AN: 67948

Other (OTH) AF: 0.501 AC: 1057 AN: 2110

Alfa AF: 0.472 Hom.: 6063

Bravo AF: 0.475

Asia WGS AF: 0.571 AC: 1986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.62
PhyloP100		-0.35
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: rs7041446; hg19: chr9-137776054;