rs3124954

Positions:

• chr9-134881650-C-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.100+729C>T		intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.100+729C>T		intron_variant
FCN2	XM_006717015.5	c.68-1652C>T		intron_variant
FCN2	XM_011518392.4	c.68-876C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.100+729C>T		intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.100+729C>T		intron_variant		5

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

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.331

Gnomad4 SAS AF: 0.428

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.352

Alfa AF: 0.343 Hom.: 3827

Bravo AF: 0.312

Asia WGS AF: 0.376 AC: 1306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs3124954; hg19: chr9-137773496;