rs375573892

Positions:

• chr9-134909506-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002003.5(FCN1):​c.*292T>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 0.0018 in 1,344,240 control chromosomes in the GnomAD database, including 3 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 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (3 hom.)
• Consequence: FCN1 NM_002003.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN1	NM_002003.5	c.*292T>C		3_prime_UTR_variant	9/9	ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.*292T>C		3_prime_UTR_variant	9/9	1	NM_002003.5	ENSP00000360871	P1

Frequencies

GnomAD3 genomes AF: 0.000867 AC: 132 AN: 152172 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00101 AC: 139 AN: 138056 Hom.: 1 AF XY: 0.00105 AC XY: 79 AN XY: 74886

Gnomad AFR exome AF: 0.000154

Gnomad AMR exome AF: 0.000245

Gnomad ASJ exome AF: 0.000361

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00142

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00169

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00192 AC: 2287 AN: 1191950 Hom.: 3 Cov.: 33 AF XY: 0.00189 AC XY: 1106 AN XY: 585176

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000235

Gnomad4 ASJ exome AF: 0.000488

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00214

Gnomad4 OTH exome AF: 0.00174

GnomAD4 genome AF: 0.000867 AC: 132 AN: 152290 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74466

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00137 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.52
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs375573892; hg19: chr9-137801352;