rs7024491

Positions:

• chr9-134883238-A-G
• chr9-134883238-A-T

Variant summary

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

The NM_004108.3(FCN2):​c.215-64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,335,638 control chromosomes in the GnomAD database, including 123,903 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 0.44 (15273 hom., cov: 32)
  • Exomes 𝑓: 0.43 (108630 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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 (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3	c.215-64A>G		intron_variant		ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.101-64A>G		intron_variant			NP_056652.1
FCN2	XM_011518392.4	c.182-64A>G		intron_variant			XP_011516694.1
FCN2	XM_006717015.5	c.68-64A>G		intron_variant			XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.215-64A>G		intron_variant		1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.101-64A>G		intron_variant		5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67585 AN: 151996 Hom.: 15252 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.415

GnomAD4 exome AF: 0.427 AC: 504950 AN: 1183524 Hom.: 108630 AF XY: 0.424 AC XY: 255413 AN XY: 602320

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.312

Gnomad4 EAS exome AF: 0.555

Gnomad4 SAS exome AF: 0.403

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.423

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.445 AC: 67659 AN: 152114 Hom.: 15273 Cov.: 32 AF XY: 0.445 AC XY: 33111 AN XY: 74358

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.412

Alfa AF: 0.409 Hom.: 12682

Bravo AF: 0.450

Asia WGS AF: 0.474 AC: 1651 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	2.3
DANN	Benign	0.57

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: rs7024491; hg19: chr9-137775084; COSMIC: COSV52478364;