rs34789496

Positions:

• chr9-134885881-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.543C>T	p.His181His	synonymous_variant	6/8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.429C>T	p.His143His	synonymous_variant	5/7		NP_056652.1
FCN2	XM_011518392.4	c.510C>T	p.His170His	synonymous_variant	6/8		XP_011516694.1
FCN2	XM_006717015.5	c.396C>T	p.His132His	synonymous_variant	5/7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.543C>T	p.His181His	synonymous_variant	6/8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.429C>T	p.His143His	synonymous_variant	5/7	5		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

GnomAD3 exomes AF: 0.0304 AC: 7586 AN: 249476 Hom.: 439 AF XY: 0.0257 AC XY: 3474 AN XY: 134988

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 SAS exome AF: 0.00878

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

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.174

Gnomad4 SAS exome AF: 0.00891

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.000712

Gnomad4 OTH exome AF: 0.0142

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

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0886

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.0107

Gnomad4 NFE AF: 0.00163

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00609 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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.53
DANN	Benign	0.44

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: rs34789496; hg19: chr9-137777727; COSMIC: COSV52477815;