rs4520243

Variant names:

• chr9-134883309-T-C
• rs4520243
• NM_004108.3:c.222T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004108.3(FCN2):​c.222T>C​(p.Arg74Arg) 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
• Publications: 21 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 -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 rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.222T>C	p.Arg74Arg	synonymous_variant	Exon 3 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.108T>C	p.Arg36Arg	synonymous_variant	Exon 2 of 7		NP_056652.1
FCN2	XM_011518392.4	c.189T>C	p.Arg63Arg	synonymous_variant	Exon 3 of 8		XP_011516694.1
FCN2	XM_006717015.5	c.75T>C	p.Arg25Arg	synonymous_variant	Exon 2 of 7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.222T>C	p.Arg74Arg	synonymous_variant	Exon 3 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.108T>C	p.Arg36Arg	synonymous_variant	Exon 2 of 7	5		ENSP00000291741.5

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

GnomAD2 exomes AF: 0.361 AC: 90470 AN: 250896 AF XY: 0.368

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 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

African (AFR) AF: 0.329 AC: 10947 AN: 33292

American (AMR) AF: 0.275 AC: 12317 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 12190 AN: 26072

East Asian (EAS) AF: 0.400 AC: 15868 AN: 39654

South Asian (SAS) AF: 0.428 AC: 36866 AN: 86066

European-Finnish (FIN) AF: 0.367 AC: 19594 AN: 53332

Middle Eastern (MID) AF: 0.412 AC: 2371 AN: 5752

European-Non Finnish (NFE) AF: 0.343 AC: 378859 AN: 1104128

Other (OTH) AF: 0.369 AC: 22174 AN: 60108

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

African (AFR) AF: 0.333 AC: 13799 AN: 41450

American (AMR) AF: 0.318 AC: 4865 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2172 AN: 5138

South Asian (SAS) AF: 0.436 AC: 2098 AN: 4814

European-Finnish (FIN) AF: 0.371 AC: 3932 AN: 10590

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

European-Non Finnish (NFE) AF: 0.343 AC: 23286 AN: 67940

Other (OTH) AF: 0.377 AC: 796 AN: 2112

Alfa AF: 0.349 Hom.: 27360

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
PhyloP100		-3.9
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: rs4520243; hg19: chr9-137775155; COSMIC: COSV52477157;