rs4520243

chr9-134883309-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004108.3(FCN2):c.222T>C(p.Arg74=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,605,134 control chromosomes in the GnomAD database, including 101,571 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 0.35 (9306 hom., cov: 32)
  • Exomes 𝑓: 0.35 (92265 hom.)
• Consequence: FCN2 NM_004108.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.88

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-3.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.222T>C	p.Arg74=	synonymous_variant	3/8	ENST00000291744.11
FCN2	NM_015837.3	c.108T>C	p.Arg36=	synonymous_variant	2/7
FCN2	XM_011518392.4	c.189T>C	p.Arg63=	synonymous_variant	3/8
FCN2	XM_006717015.5	c.75T>C	p.Arg25=	synonymous_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.222T>C	p.Arg74=	synonymous_variant	3/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.108T>C	p.Arg36=	synonymous_variant	2/7	5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52819 AN: 151900 Hom.: 9296 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.372

GnomAD3 exomes AF: 0.361 AC: 90470 AN: 250896 Hom.: 16912 AF XY: 0.368 AC XY: 49919 AN XY: 135714

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.436

Gnomad SAS exome AF: 0.435

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.352 AC: 511186 AN: 1453118 Hom.: 92265 Cov.: 35 AF XY: 0.354 AC XY: 256172 AN XY: 723342

Gnomad4 AFR exome AF: 0.329

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.468

Gnomad4 EAS exome AF: 0.400

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.367

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.369

GnomAD4 genome AF: 0.348 AC: 52852 AN: 152016 Hom.: 9306 Cov.: 32 AF XY: 0.348 AC XY: 25857 AN XY: 74304

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.377

Alfa AF: 0.353 Hom.: 18086

Bravo AF: 0.344

Asia WGS AF: 0.416 AC: 1445 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.15
Dann	Benign	0.52

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: rs4520243; hg19: chr9-137775155; COSMIC: COSV52477157;