rs28909976

Variant names:

• chr9-134918142-CA-C
• rs28909976
• NM_002003.5:c.-272delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_002003.5(FCN1):​c.-272delT variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (21959 hom., cov: 0)
• Consequence: FCN1 NM_002003.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.709
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5	c.-272delT		upstream_gene_variant		ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.-272delT		upstream_gene_variant		1	NM_002003.5	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79286 AN: 151826 Hom.: 21965 Cov.: 0

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.621

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.522 AC: 79294 AN: 151944 Hom.: 21959 Cov.: 0 AF XY: 0.526 AC XY: 39031 AN XY: 74250

African (AFR) AF: 0.337 AC: 13982 AN: 41442

American (AMR) AF: 0.453 AC: 6918 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.621 AC: 2153 AN: 3468

East Asian (EAS) AF: 0.429 AC: 2211 AN: 5156

South Asian (SAS) AF: 0.573 AC: 2750 AN: 4802

European-Finnish (FIN) AF: 0.657 AC: 6929 AN: 10550

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.624 AC: 42377 AN: 67944

Other (OTH) AF: 0.512 AC: 1080 AN: 2110

Alfa AF: 0.451 Hom.: 1367

Bravo AF: 0.494

Asia WGS AF: 0.458 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs28909976; hg19: chr9-137809988;