rs3128624

chr9-134883293-A-Gchr9-134883293-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.215-9A>G variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001236
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.215-9A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.101-9A>G		splice_polypyrimidine_tract_variant, intron_variant
FCN2	XM_006717015.5	c.68-9A>G		splice_polypyrimidine_tract_variant, intron_variant
FCN2	XM_011518392.4	c.182-9A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.215-9A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.101-9A>G		splice_polypyrimidine_tract_variant, intron_variant		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

GnomAD3 exomes AF: 0.361 AC: 90600 AN: 250944 Hom.: 16968 AF XY: 0.368 AC XY: 49967 AN XY: 135738

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 SAS exome AF: 0.435

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

Gnomad4 AFR exome AF: 0.327

Gnomad4 AMR exome AF: 0.275

Gnomad4 ASJ exome AF: 0.467

Gnomad4 EAS exome AF: 0.407

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.369

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

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.378

Alfa AF: 0.354 Hom.: 9714

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	9.0
Dann	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs3128624; hg19: chr9-137775139; COSMIC: COSV52477148;