rs2989721

chr9-134914488-A-G

Variant summary

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

The NM_002003.5(FCN1):c.272-68T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 1,495,954 control chromosomes in the GnomAD database, including 291,277 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 0.63 (30130 hom., cov: 33)
  • Exomes 𝑓: 0.62 (261147 hom.)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN1	NM_002003.5	c.272-68T>C		intron_variant		ENST00000371806.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN1	ENST00000371806.4	c.272-68T>C		intron_variant		1	NM_002003.5	P1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95096 AN: 151194 Hom.: 30120 Cov.: 33

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.694

Gnomad FIN AF: 0.654

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.589

GnomAD4 exome AF: 0.621 AC: 834630 AN: 1344638 Hom.: 261147 AF XY: 0.625 AC XY: 421983 AN XY: 675678

Gnomad4 AFR exome AF: 0.702

Gnomad4 AMR exome AF: 0.393

Gnomad4 ASJ exome AF: 0.620

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.704

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.627

Gnomad4 OTH exome AF: 0.616

GnomAD4 genome AF: 0.629 AC: 95156 AN: 151316 Hom.: 30130 Cov.: 33 AF XY: 0.629 AC XY: 46489 AN XY: 73914

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.481

Gnomad4 SAS AF: 0.692

Gnomad4 FIN AF: 0.654

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.587

Alfa AF: 0.635 Hom.: 3764

Bravo AF: 0.614

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.46
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs2989721; hg19: chr9-137806334;