rs2070620

Positions:

• chr9-134914222-C-T

Variant summary

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

The NM_002003.5(FCN1):​c.307+163G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 152,206 control chromosomes in the GnomAD database, including 2,131 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 0.097 (2131 hom., cov: 33)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN1	NM_002003.5	c.307+163G>A		intron_variant		ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.307+163G>A		intron_variant		1	NM_002003.5	ENSP00000360871	P1

Frequencies

GnomAD3 genomes AF: 0.0969 AC: 14737 AN: 152088 Hom.: 2125 Cov.: 33

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0375

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.0544

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0679

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0971 AC: 14781 AN: 152206 Hom.: 2131 Cov.: 33 AF XY: 0.0939 AC XY: 6990 AN XY: 74426

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00237

Gnomad4 OTH AF: 0.0682

Alfa AF: 0.0946 Hom.: 384

Bravo AF: 0.108

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.67

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: rs2070620; hg19: chr9-137806068; COSMIC: COSV65663116;