9-134914641-G-C

Position:

• chr9-134914641-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002003.5(FCN1):​c.271+115C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 924,756 control chromosomes in the GnomAD database, including 1 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 0.00037 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00030 (1 hom.)
• Consequence: FCN1 NM_002003.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN1	NM_002003.5	c.271+115C>G		intron_variant		ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.271+115C>G		intron_variant		1	NM_002003.5	ENSP00000360871.3

Frequencies

GnomAD3 genomes AF: 0.000369 AC: 56 AN: 151788 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000948

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.000960

GnomAD4 exome AF: 0.000298 AC: 230 AN: 772852 Hom.: 1 AF XY: 0.000267 AC XY: 106 AN XY: 397326

Gnomad4 AFR exome AF: 0.000161

Gnomad4 AMR exome AF: 0.000331

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000144

Gnomad4 FIN exome AF: 0.000254

Gnomad4 NFE exome AF: 0.000318

Gnomad4 OTH exome AF: 0.000574

GnomAD4 genome AF: 0.000369 AC: 56 AN: 151904 Hom.: 0 Cov.: 30 AF XY: 0.000377 AC XY: 28 AN XY: 74212

Gnomad4 AFR AF: 0.000121

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000948

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.000950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.23
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs2989722; hg19: chr9-137806487;