9-134912984-G-C

Variant names:

• chr9-134912984-G-C
• rs2070622
• NM_002003.5:c.468+32C>G

Variant summary

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

The NM_002003.5(FCN1):​c.468+32C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,596,904 control chromosomes in the GnomAD database, including 323,083 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 0.68 (36368 hom., cov: 33)
  • Exomes 𝑓: 0.63 (286715 hom.)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.504

Genes affected

FCN1 (HGNC:3623): (ficolin 1) The ficolin family of proteins are 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. The collagen-like and the fibrinogen-like domains are also found separately in other proteins such as complement protein C1q, C-type lectins known as collectins, and tenascins. However, all these proteins recognize different targets, and are functionally distinct. Ficolin 1 encoded by FCN1 is predominantly expressed in the peripheral blood leukocytes, and has been postulated to function as a plasma protein with elastin-binding activity. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5	c.468+32C>G		intron_variant	Intron 6 of 8	ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.468+32C>G		intron_variant	Intron 6 of 8	1	NM_002003.5	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.681 AC: 103459 AN: 151994 Hom.: 36334 Cov.: 33

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.817

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.486

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.629

GnomAD3 exomes AF: 0.615 AC: 137646 AN: 223858 Hom.: 43838 AF XY: 0.624 AC XY: 75749 AN XY: 121320

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.627

Gnomad EAS exome AF: 0.483

Gnomad SAS exome AF: 0.713

Gnomad FIN exome AF: 0.650

Gnomad NFE exome AF: 0.635

Gnomad OTH exome AF: 0.607

GnomAD4 exome AF: 0.626 AC: 904923 AN: 1444792 Hom.: 286715 Cov.: 43 AF XY: 0.630 AC XY: 451634 AN XY: 717276

Gnomad4 AFR exome AF: 0.875

Gnomad4 AMR exome AF: 0.411

Gnomad4 ASJ exome AF: 0.624

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.714

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.626

Gnomad4 OTH exome AF: 0.630

GnomAD4 genome AF: 0.681 AC: 103541 AN: 152112 Hom.: 36368 Cov.: 33 AF XY: 0.679 AC XY: 50510 AN XY: 74364

Gnomad4 AFR AF: 0.859

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.485

Gnomad4 SAS AF: 0.702

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.626

Alfa AF: 0.586 Hom.: 3286

Bravo AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.76

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: rs2070622; hg19: chr9-137804830; COSMIC: COSV65662682;