9-134883238-A-G

Variant names:

• chr9-134883238-A-G
• rs7024491
• NM_004108.3:c.215-64A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.215-64A>G		intron_variant	Intron 2 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.101-64A>G		intron_variant	Intron 1 of 6		NP_056652.1
FCN2	XM_011518392.4	c.182-64A>G		intron_variant	Intron 2 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-64A>G		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.215-64A>G		intron_variant	Intron 2 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.101-64A>G		intron_variant	Intron 1 of 6	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

African (AFR) AF: 0.535 AC: 15009 AN: 28028

American (AMR) AF: 0.464 AC: 20606 AN: 44366

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 7501 AN: 24056

East Asian (EAS) AF: 0.555 AC: 21295 AN: 38346

South Asian (SAS) AF: 0.403 AC: 32357 AN: 80348

European-Finnish (FIN) AF: 0.399 AC: 21185 AN: 53074

Middle Eastern (MID) AF: 0.368 AC: 1906 AN: 5180

European-Non Finnish (NFE) AF: 0.423 AC: 363822 AN: 859150

Other (OTH) AF: 0.417 AC: 21269 AN: 50976

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

African (AFR) AF: 0.518 AC: 21491 AN: 41502

American (AMR) AF: 0.453 AC: 6921 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1078 AN: 3468

East Asian (EAS) AF: 0.543 AC: 2790 AN: 5142

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4822

European-Finnish (FIN) AF: 0.403 AC: 4267 AN: 10588

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27617 AN: 67996

Other (OTH) AF: 0.412 AC: 868 AN: 2106

Alfa AF: 0.419 Hom.: 37403

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
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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