rs34789496

Variant names:

• chr9-134885881-C-T
• rs34789496
• NM_004108.3:c.543C>T

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.543C>T​(p.His181His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,613,114 control chromosomes in the GnomAD database, including 1,110 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 0.019 (165 hom., cov: 32)
  • Exomes 𝑓: 0.011 (945 hom.)
• Consequence: FCN2 NM_004108.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.19
• Publications: 9 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=-0.78).
• BP7: Synonymous conserved (PhyloP=-2.19 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.543C>T	p.His181His	synonymous	Exon 6 of 8	NP_004099.2
	FCN2	NM_015837.3		c.429C>T	p.His143His	synonymous	Exon 5 of 7	NP_056652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.543C>T	p.His181His	synonymous	Exon 6 of 8	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.429C>T	p.His143His	synonymous	Exon 5 of 7	ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2948 AN: 151922 Hom.: 160 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0879

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.0135

Gnomad FIN AF: 0.0107

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00163

Gnomad OTH AF: 0.0206

GnomAD2 exomes AF: 0.0304 AC: 7586 AN: 249476 AF XY: 0.0257

Gnomad AFR exome AF: 0.0116

Gnomad AMR exome AF: 0.111

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.138

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.00139

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0106 AC: 15528 AN: 1461074 Hom.: 945 Cov.: 32 AF XY: 0.0102 AC XY: 7380 AN XY: 726834

African (AFR) AF: 0.0107 AC: 357 AN: 33470

American (AMR) AF: 0.107 AC: 4800 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 497 AN: 26066

East Asian (EAS) AF: 0.174 AC: 6905 AN: 39678

South Asian (SAS) AF: 0.00891 AC: 768 AN: 86208

European-Finnish (FIN) AF: 0.0101 AC: 537 AN: 53240

Middle Eastern (MID) AF: 0.00278 AC: 16 AN: 5760

European-Non Finnish (NFE) AF: 0.000712 AC: 792 AN: 1111630

Other (OTH) AF: 0.0142 AC: 856 AN: 60356

GnomAD4 genome AF: 0.0195 AC: 2962 AN: 152040 Hom.: 165 Cov.: 32 AF XY: 0.0232 AC XY: 1720 AN XY: 74296

African (AFR) AF: 0.0118 AC: 492 AN: 41530

American (AMR) AF: 0.0886 AC: 1354 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3468

East Asian (EAS) AF: 0.143 AC: 725 AN: 5070

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4808

European-Finnish (FIN) AF: 0.0107 AC: 114 AN: 10608

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00163 AC: 111 AN: 67952

Other (OTH) AF: 0.0194 AC: 41 AN: 2108

Alfa AF: 0.00619 Hom.: 11

Bravo AF: 0.0245

Asia WGS AF: 0.0750 AC: 261 AN: 3478

EpiCase AF: 0.000872

EpiControl AF: 0.00190

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.44
PhyloP100		-2.2
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: rs34789496; hg19: chr9-137777727; COSMIC: COSV52477815;