NM_004108.3:c.214+270C>T

Variant names:

• chr9-134882909-C-T
• rs73565979
• NM_004108.3:c.214+270C>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.214+270C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,568 control chromosomes in the GnomAD database, including 1,396 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 0.13 (1396 hom., cov: 33)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.214+270C>T		intron_variant	Intron 2 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.101-393C>T		intron_variant	Intron 1 of 6		NP_056652.1
FCN2	XM_011518392.4	c.181+270C>T		intron_variant	Intron 2 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-393C>T		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.214+270C>T		intron_variant	Intron 2 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.101-393C>T		intron_variant	Intron 1 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19937 AN: 151454 Hom.: 1393 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0415

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.132 AC: 19961 AN: 151568 Hom.: 1396 Cov.: 33 AF XY: 0.130 AC XY: 9624 AN XY: 74098

African (AFR) AF: 0.187 AC: 7658 AN: 40866

American (AMR) AF: 0.119 AC: 1816 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0415 AC: 144 AN: 3470

East Asian (EAS) AF: 0.180 AC: 929 AN: 5172

South Asian (SAS) AF: 0.120 AC: 581 AN: 4832

European-Finnish (FIN) AF: 0.0945 AC: 1002 AN: 10608

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7532 AN: 68018

Other (OTH) AF: 0.127 AC: 269 AN: 2110

Alfa AF: 0.134 Hom.: 193

Bravo AF: 0.136

Asia WGS AF: 0.153 AC: 533 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.089
DANN	Benign	0.52
PhyloP100		-1.2
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: rs73565979; hg19: chr9-137774755;