9-134881772-C-T

Variant summary

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

The NM_004108.3(FCN2):c.101-754C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 152,030 control chromosomes in the GnomAD database, including 7,786 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 0.31 (7786 hom., cov: 32)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.101-754C>T		intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.100+851C>T		intron_variant
FCN2	XM_006717015.5	c.68-1530C>T		intron_variant
FCN2	XM_011518392.4	c.68-754C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.101-754C>T		intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.100+851C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47519 AN: 151912 Hom.: 7782 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.313 AC: 47528 AN: 152030 Hom.: 7786 Cov.: 32 AF XY: 0.312 AC XY: 23203 AN XY: 74304

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.332

Gnomad4 SAS AF: 0.387

Gnomad4 FIN AF: 0.377

Gnomad4 NFE AF: 0.353

Gnomad4 OTH AF: 0.346

Alfa AF: 0.335 Hom.: 4645

Bravo AF: 0.304

Asia WGS AF: 0.352 AC: 1221 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.44
Dann	Benign	0.65

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: rs3128625; hg19: chr9-137773618;