9-134908401-A-G

Variant names:

• chr9-134908401-A-G
• rs1537189
• NM_002003.5:c.*1397T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002003.5(FCN1):​c.*1397T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,114 control chromosomes in the GnomAD database, including 36,324 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 (36320 hom., cov: 32)
  • Exomes 𝑓: 0.75 (4 hom.)
• Consequence: FCN1 NM_002003.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• 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.*1397T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.*1397T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_002003.5	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103386 AN: 151980 Hom.: 36285 Cov.: 32

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.672

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.750 AC: 12 AN: 16 Hom.: 4 Cov.: 0 AF XY: 0.700 AC XY: 7 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.750 AC: 6 AN: 8

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.680 AC: 103469 AN: 152098 Hom.: 36320 Cov.: 32 AF XY: 0.679 AC XY: 50466 AN XY: 74342

African (AFR) AF: 0.859 AC: 35637 AN: 41508

American (AMR) AF: 0.515 AC: 7872 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2095 AN: 3472

East Asian (EAS) AF: 0.490 AC: 2534 AN: 5176

South Asian (SAS) AF: 0.701 AC: 3377 AN: 4816

European-Finnish (FIN) AF: 0.657 AC: 6952 AN: 10576

Middle Eastern (MID) AF: 0.675 AC: 197 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42739 AN: 67966

Other (OTH) AF: 0.627 AC: 1321 AN: 2108

Alfa AF: 0.636 Hom.: 79364

Bravo AF: 0.671

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs1537189; hg19: chr9-137800247;