9-134882719-G-C

Position:

• chr9-134882719-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004108.3(FCN2):​c.214+80G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 999,720 control chromosomes in the GnomAD database, including 11 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 0.0048 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00066 (6 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

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=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00483 (736/152304) while in subpopulation AFR AF= 0.0167 (692/41554). AF 95% confidence interval is 0.0156. There are 5 homozygotes in gnomad4. There are 342 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.214+80G>C		intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.101-583G>C		intron_variant
FCN2	XM_006717015.5	c.68-583G>C		intron_variant
FCN2	XM_011518392.4	c.181+80G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.214+80G>C		intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.101-583G>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00484 AC: 736 AN: 152186 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000662 AC: 561 AN: 847416 Hom.: 6 AF XY: 0.000565 AC XY: 249 AN XY: 440938

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000296

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000384

Gnomad4 OTH exome AF: 0.00153

GnomAD4 genome AF: 0.00483 AC: 736 AN: 152304 Hom.: 5 Cov.: 33 AF XY: 0.00459 AC XY: 342 AN XY: 74488

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000978 Hom.: 0

Bravo AF: 0.00580

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.64
DANN	Benign	0.34

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: rs75577478; hg19: chr9-137774565;