9-134910318-C-G

Variant names:

• chr9-134910318-C-G
• rs1888710
• NM_002003.5:c.734-273G>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.734-273G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,952 control chromosomes in the GnomAD database, including 36,187 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 (36187 hom., cov: 31)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 2 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 = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5	c.734-273G>C		intron_variant	Intron 8 of 8	ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.734-273G>C		intron_variant	Intron 8 of 8	1	NM_002003.5	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103153 AN: 151834 Hom.: 36152 Cov.: 31

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.603

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.679 AC: 103236 AN: 151952 Hom.: 36187 Cov.: 31 AF XY: 0.678 AC XY: 50335 AN XY: 74252

African (AFR) AF: 0.857 AC: 35500 AN: 41446

American (AMR) AF: 0.514 AC: 7859 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 2090 AN: 3464

East Asian (EAS) AF: 0.488 AC: 2507 AN: 5136

South Asian (SAS) AF: 0.702 AC: 3379 AN: 4816

European-Finnish (FIN) AF: 0.657 AC: 6949 AN: 10574

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42693 AN: 67912

Other (OTH) AF: 0.625 AC: 1319 AN: 2110

Alfa AF: 0.542 Hom.: 1498

Bravo AF: 0.671

Asia WGS AF: 0.599 AC: 2083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1888710; hg19: chr9-137802164;