chr9-134880758-A-T

Variant names:

• chr9-134880758-A-T
• rs7865453
• XM_011518392.4:c.68-1768A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The XM_011518392.4(FCN2):​c.68-1768A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,297,506 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000047 (0 hom.)
• Consequence: FCN2 XM_011518392.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	XM_011518392.4	c.68-1768A>T		intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-2544A>T		intron_variant	Intron 1 of 6		XP_006717078.1
FCN2	NM_004108.3	c.-64A>T		upstream_gene_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.-64A>T		upstream_gene_variant			NP_056652.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.-64A>T		upstream_gene_variant		1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.-64A>T		upstream_gene_variant		5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152134 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000471 AC: 54 AN: 1145372 Hom.: 0 AF XY: 0.0000533 AC XY: 31 AN XY: 581584

Gnomad4 AFR exome AF: 0.0000369

Gnomad4 AMR exome AF: 0.0000734

Gnomad4 ASJ exome AF: 0.0000423

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000564

Gnomad4 OTH exome AF: 0.0000402

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152134 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74324

Gnomad4 AFR AF: 0.0000242

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000453

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.9
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7865453; hg19: chr9-137772604;