9-134914641-G-A

Variant names:

• chr9-134914641-G-A
• rs2989722
• NM_002003.5:c.271+115C>T

Variant summary

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

The NM_002003.5(FCN1):​c.271+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 923,456 control chromosomes in the GnomAD database, including 162,056 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 0.52 (21997 hom., cov: 30)
  • Exomes 𝑓: 0.60 (140059 hom.)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002003.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	NM_002003.5	MANE Select	c.271+115C>T		intron	N/A	NP_001994.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	ENST00000371806.4	TSL:1 MANE Select	c.271+115C>T		intron	N/A	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79321 AN: 151704 Hom.: 22005 Cov.: 30

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.510

GnomAD4 exome AF: 0.598 AC: 461595 AN: 771636 Hom.: 140059 AF XY: 0.601 AC XY: 238609 AN XY: 396742

African (AFR) AF: 0.339 AC: 6301 AN: 18614

American (AMR) AF: 0.381 AC: 11482 AN: 30132

Ashkenazi Jewish (ASJ) AF: 0.610 AC: 11435 AN: 18758

East Asian (EAS) AF: 0.399 AC: 12975 AN: 32528

South Asian (SAS) AF: 0.609 AC: 38115 AN: 62620

European-Finnish (FIN) AF: 0.641 AC: 30226 AN: 47186

Middle Eastern (MID) AF: 0.588 AC: 2115 AN: 3596

European-Non Finnish (NFE) AF: 0.629 AC: 328056 AN: 521670

Other (OTH) AF: 0.572 AC: 20890 AN: 36532

GnomAD4 genome AF: 0.523 AC: 79327 AN: 151820 Hom.: 21997 Cov.: 30 AF XY: 0.526 AC XY: 39039 AN XY: 74172

African (AFR) AF: 0.339 AC: 14052 AN: 41418

American (AMR) AF: 0.450 AC: 6872 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2135 AN: 3466

East Asian (EAS) AF: 0.429 AC: 2190 AN: 5108

South Asian (SAS) AF: 0.584 AC: 2804 AN: 4804

European-Finnish (FIN) AF: 0.657 AC: 6927 AN: 10538

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42388 AN: 67906

Other (OTH) AF: 0.507 AC: 1067 AN: 2106

Alfa AF: 0.443 Hom.: 1432

Bravo AF: 0.494

Asia WGS AF: 0.467 AC: 1625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.34
PhyloP100		-2.0
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: rs2989722; hg19: chr9-137806487;