9-134883293-A-G

Variant names:

• chr9-134883293-A-G
• rs3128624
• NM_004108.3:c.215-9A>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.215-9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 1,595,166 control chromosomes in the GnomAD database, including 100,983 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 0.35 (9328 hom., cov: 32)
  • Exomes 𝑓: 0.35 (91655 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Scores: Splicing: ADA: 0.00001236
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• Publications: 13 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.215-9A>G		intron	N/A	NP_004099.2
	FCN2	NM_015837.3		c.101-9A>G		intron	N/A	NP_056652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.215-9A>G		intron	N/A	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.101-9A>G		intron	N/A	ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52879 AN: 151868 Hom.: 9318 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.361 AC: 90600 AN: 250944 AF XY: 0.368

Gnomad AFR exome AF: 0.335

Gnomad AMR exome AF: 0.266

Gnomad ASJ exome AF: 0.467

Gnomad EAS exome AF: 0.444

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.351

Gnomad OTH exome AF: 0.363

GnomAD4 exome AF: 0.350 AC: 505688 AN: 1443180 Hom.: 91655 Cov.: 33 AF XY: 0.353 AC XY: 253724 AN XY: 718934

African (AFR) AF: 0.327 AC: 10818 AN: 33076

American (AMR) AF: 0.275 AC: 12304 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 12144 AN: 25990

East Asian (EAS) AF: 0.407 AC: 16110 AN: 39594

South Asian (SAS) AF: 0.428 AC: 36727 AN: 85856

European-Finnish (FIN) AF: 0.368 AC: 19605 AN: 53340

Middle Eastern (MID) AF: 0.411 AC: 2357 AN: 5740

European-Non Finnish (NFE) AF: 0.341 AC: 373552 AN: 1095146

Other (OTH) AF: 0.369 AC: 22071 AN: 59742

GnomAD4 genome AF: 0.348 AC: 52912 AN: 151986 Hom.: 9328 Cov.: 32 AF XY: 0.348 AC XY: 25887 AN XY: 74290

African (AFR) AF: 0.333 AC: 13812 AN: 41462

American (AMR) AF: 0.318 AC: 4862 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3470

East Asian (EAS) AF: 0.435 AC: 2229 AN: 5130

South Asian (SAS) AF: 0.436 AC: 2094 AN: 4806

European-Finnish (FIN) AF: 0.372 AC: 3933 AN: 10578

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23281 AN: 67944

Other (OTH) AF: 0.378 AC: 797 AN: 2110

Alfa AF: 0.351 Hom.: 12478

Bravo AF: 0.344

Asia WGS AF: 0.424 AC: 1473 AN: 3478

EpiCase AF: 0.357

EpiControl AF: 0.359

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	9.0
DANN	Benign	0.47
PhyloP100		-0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000012
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.010		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: rs3128624; hg19: chr9-137775139; COSMIC: COSV52477148;