9-134887041-T-G

Position:

• chr9-134887041-T-G

Variant summary

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

The NM_004108.3(FCN2):​c.695-127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 1,079,162 control chromosomes in the GnomAD database, including 8,106 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 0.14 (1472 hom., cov: 33)
  • Exomes 𝑓: 0.12 (6634 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.62

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.695-127T>G		intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.581-127T>G		intron_variant
FCN2	XM_006717015.5	c.548-127T>G		intron_variant
FCN2	XM_011518392.4	c.662-127T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.695-127T>G		intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.581-127T>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20565 AN: 152120 Hom.: 1472 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.115 AC: 106680 AN: 926924 Hom.: 6634 AF XY: 0.115 AC XY: 55265 AN XY: 482612

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0467

Gnomad4 EAS exome AF: 0.158

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.110

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.135 AC: 20589 AN: 152238 Hom.: 1472 Cov.: 33 AF XY: 0.133 AC XY: 9928 AN XY: 74438

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0947

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.131

Alfa AF: 0.0720 Hom.: 133

Bravo AF: 0.141

Asia WGS AF: 0.154 AC: 539 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.78

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: rs7872508; hg19: chr9-137778887;