9-134917839-C-A

Position:

• chr9-134917839-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002003.5(FCN1):​c.33G>T​(p.Gly11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 1,612,054 control chromosomes in the GnomAD database, including 82,141 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 0.31 (7564 hom., cov: 32)
  • Exomes 𝑓: 0.31 (74577 hom.)
• Consequence: FCN1 NM_002003.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN1	NM_002003.5	c.33G>T	p.Gly11=	synonymous_variant	1/9	ENST00000371806.4	NP_001994.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4	c.33G>T	p.Gly11=	synonymous_variant	1/9	1	NM_002003.5	ENSP00000360871	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47436 AN: 151874 Hom.: 7560 Cov.: 32

Gnomad AFR AF: 0.313

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.338

Gnomad OTH AF: 0.303

GnomAD3 exomes AF: 0.281 AC: 70571 AN: 251088 Hom.: 10851 AF XY: 0.283 AC XY: 38470 AN XY: 135728

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.163

Gnomad ASJ exome AF: 0.328

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.215

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.338

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.314 AC: 459169 AN: 1460062 Hom.: 74577 Cov.: 32 AF XY: 0.313 AC XY: 227123 AN XY: 726434

Gnomad4 AFR exome AF: 0.316

Gnomad4 AMR exome AF: 0.171

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.112

Gnomad4 SAS exome AF: 0.221

Gnomad4 FIN exome AF: 0.340

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.303

GnomAD4 genome AF: 0.312 AC: 47449 AN: 151992 Hom.: 7564 Cov.: 32 AF XY: 0.309 AC XY: 22920 AN XY: 74268

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.338

Gnomad4 OTH AF: 0.299

Alfa AF: 0.315 Hom.: 10081

Bravo AF: 0.305

Asia WGS AF: 0.166 AC: 580 AN: 3478

EpiCase AF: 0.333

EpiControl AF: 0.337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.22
DANN	Benign	0.38

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: rs10858293; hg19: chr9-137809685; COSMIC: COSV65662299;