rs12344051

Variant names:

• chr9-134880608-G-A
• rs12344051
• XM_011518392.4:c.68-1918G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The XM_011518392.4(FCN2):​c.68-1918G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 152,240 control chromosomes in the GnomAD database, including 33 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 0.011 (33 hom., cov: 33)
• Consequence: FCN2 XM_011518392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.850
• Publications: 1 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=-0.94).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0113 (1717/152240) while in subpopulation AFR AF = 0.0367 (1523/41540). AF 95% confidence interval is 0.0351. There are 33 homozygotes in GnomAd4. There are 807 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	XM_011518392.4	c.68-1918G>A		intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-2694G>A		intron_variant	Intron 1 of 6		XP_006717078.1
FCN2	NM_004108.3	c.-214G>A		upstream_gene_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.-214G>A		upstream_gene_variant			NP_056652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.-214G>A		upstream_gene_variant		1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.-214G>A		upstream_gene_variant		5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1716 AN: 152124 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0367

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.00669

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

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152240 Hom.: 33 Cov.: 33 AF XY: 0.0108 AC XY: 807 AN XY: 74436

African (AFR) AF: 0.0367 AC: 1523 AN: 41540

American (AMR) AF: 0.00562 AC: 86 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4828

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68004

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00670 Hom.: 5

Bravo AF: 0.0128

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.93
DANN	Benign	0.46
PhyloP100		-0.85
PromoterAI		0.018	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12344051; hg19: chr9-137772454; COSMIC: COSV52479452;