rs3124954

Variant names:

• chr9-134881650-C-T
• rs3124954
• NM_004108.3:c.100+729C>T

Variant summary

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

The NM_004108.3(FCN2):​c.100+729C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,982 control chromosomes in the GnomAD database, including 8,233 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 0.32 (8233 hom., cov: 32)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.130
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.412 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.100+729C>T		intron	N/A	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.100+729C>T		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.100+729C>T		intron	N/A	ENSP00000291744.6	Q15485-1
	FCN2	ENST00000855732.1		c.100+729C>T		intron	N/A	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.100+729C>T		intron	N/A	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48871 AN: 151864 Hom.: 8229 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.349

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

GnomAD4 genome AF: 0.322 AC: 48882 AN: 151982 Hom.: 8233 Cov.: 32 AF XY: 0.322 AC XY: 23887 AN XY: 74278

African (AFR) AF: 0.217 AC: 9001 AN: 41460

American (AMR) AF: 0.308 AC: 4701 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1700 AN: 5132

South Asian (SAS) AF: 0.428 AC: 2057 AN: 4808

European-Finnish (FIN) AF: 0.378 AC: 3998 AN: 10568

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24825 AN: 67950

Other (OTH) AF: 0.352 AC: 740 AN: 2102

Alfa AF: 0.341 Hom.: 4535

Bravo AF: 0.312

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.54
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3124954; hg19: chr9-137773496;