chr9-134880818-A-G

Variant names:

• chr9-134880818-A-G
• rs17514136
• NM_004108.3:c.-4A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 54 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 -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000291744.11. 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.-4A>G		5_prime_UTR	Exon 1 of 8	NP_004099.2
	FCN2	NM_015837.3		c.-4A>G		5_prime_UTR	Exon 1 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.-4A>G		5_prime_UTR	Exon 1 of 8	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.-4A>G		5_prime_UTR	Exon 1 of 7	ENSP00000291741.5

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

GnomAD2 exomes AF: 0.230 AC: 56907 AN: 247884 AF XY: 0.231

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 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

African (AFR) AF: 0.196 AC: 6542 AN: 33414

American (AMR) AF: 0.189 AC: 8438 AN: 44628

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 6220 AN: 26064

East Asian (EAS) AF: 0.0606 AC: 2404 AN: 39684

South Asian (SAS) AF: 0.210 AC: 18037 AN: 86034

European-Finnish (FIN) AF: 0.274 AC: 14524 AN: 53044

Middle Eastern (MID) AF: 0.257 AC: 1482 AN: 5762

European-Non Finnish (NFE) AF: 0.276 AC: 305610 AN: 1109098

Other (OTH) AF: 0.248 AC: 14944 AN: 60254

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

African (AFR) AF: 0.203 AC: 8445 AN: 41522

American (AMR) AF: 0.219 AC: 3348 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 871 AN: 3468

East Asian (EAS) AF: 0.0655 AC: 339 AN: 5174

South Asian (SAS) AF: 0.206 AC: 995 AN: 4826

European-Finnish (FIN) AF: 0.285 AC: 3021 AN: 10588

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18951 AN: 67974

Other (OTH) AF: 0.229 AC: 485 AN: 2114

Alfa AF: 0.257 Hom.: 4948

Bravo AF: 0.235

Asia WGS AF: 0.152 AC: 526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		-0.059
PromoterAI		-0.017	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17514136; hg19: chr9-137772664;