9-134880818-A-G

Position:

• chr9-134880818-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000291744.11(FCN2):​c.-4A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,610,128 control chromosomes in the GnomAD database, including 55,295 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 0.24 (4776 hom., cov: 33)
  • Exomes 𝑓: 0.26 (50519 hom.)
• Consequence: FCN2 ENST00000291744.11 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.-4A>G		5_prime_UTR_variant	1/8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.-4A>G		5_prime_UTR_variant	1/7		NP_056652.1
FCN2	XM_006717015.5	c.68-2484A>G		intron_variant			XP_006717078.1
FCN2	XM_011518392.4	c.68-1708A>G		intron_variant			XP_011516694.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.-4A>G		5_prime_UTR_variant	1/8	1	NM_004108.3	ENSP00000291744	P1
FCN2	ENST00000350339.3	c.-4A>G		5_prime_UTR_variant	1/7	5		ENSP00000291741

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37076 AN: 152028 Hom.: 4783 Cov.: 33

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.578

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0659

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.232

GnomAD3 exomes AF: 0.230 AC: 56907 AN: 247884 Hom.: 7088 AF XY: 0.231 AC XY: 31051 AN XY: 134270

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.183

Gnomad ASJ exome AF: 0.241

Gnomad EAS exome AF: 0.0555

Gnomad SAS exome AF: 0.204

Gnomad FIN exome AF: 0.277

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.240

GnomAD4 exome AF: 0.259 AC: 378201 AN: 1457982 Hom.: 50519 Cov.: 32 AF XY: 0.259 AC XY: 187989 AN XY: 725332

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.239

Gnomad4 EAS exome AF: 0.0606

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.248

GnomAD4 genome AF: 0.244 AC: 37069 AN: 152146 Hom.: 4776 Cov.: 33 AF XY: 0.242 AC XY: 17973 AN XY: 74370

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.0655

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.229

Alfa AF: 0.259 Hom.: 3725

Bravo AF: 0.235

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Benign	0.73

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

Publications

LitVar

Other links and lift over

dbSNP: rs17514136; hg19: chr9-137772664;