rs10441778

chr9-134916437-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002003.5(FCN1):c.128G>A(p.Gly43Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,226 control chromosomes in the GnomAD database, including 57 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 0.0098 (18 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (39 hom.)
• Consequence: FCN1 NM_002003.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.190

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005895704).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00982 (1496/152376) while in subpopulation AFR AF= 0.0335 (1394/41592). AF 95% confidence interval is 0.0321. There are 18 homozygotes in gnomad4. There are 689 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN1	NM_002003.5	c.128G>A	p.Gly43Asp	missense_variant	2/9	ENST00000371806.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN1	ENST00000371806.4	c.128G>A	p.Gly43Asp	missense_variant	2/9	1	NM_002003.5	P1

Frequencies

GnomAD3 genomes AF: 0.00981 AC: 1494 AN: 152258 Hom.: 18 Cov.: 33

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00298 AC: 749 AN: 251434 Hom.: 15 AF XY: 0.00213 AC XY: 289 AN XY: 135888

Gnomad AFR exome AF: 0.0348

Gnomad AMR exome AF: 0.00338

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000352

Gnomad OTH exome AF: 0.00358

GnomAD4 exome AF: 0.00122 AC: 1785 AN: 1461850 Hom.: 39 Cov.: 32 AF XY: 0.00109 AC XY: 793 AN XY: 727226

Gnomad4 AFR exome AF: 0.0350

Gnomad4 AMR exome AF: 0.00380

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.000208

Gnomad4 OTH exome AF: 0.00293

GnomAD4 genome AF: 0.00982 AC: 1496 AN: 152376 Hom.: 18 Cov.: 33 AF XY: 0.00925 AC XY: 689 AN XY: 74516

Gnomad4 AFR AF: 0.0335

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00481 Hom.: 4

Bravo AF: 0.0113

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0354 AC: 156

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00352 AC: 427

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.22
Cadd	Benign	14
Dann	Uncertain	0.99
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.83	T;T
MetaRNN	Benign	0.0059	T;T
MetaSVM	Uncertain	-0.11	T
MutationTaster	Benign	0.95	N
PrimateAI	Benign	0.43	T
Sift4G	Uncertain	0.019	D;T
Polyphen		0.058	.;B
Vest4		0.13
MVP		0.94
MPC		0.18
ClinPred		0.013	T
GERP RS		3.0
Varity_R		0.11
gMVP		0.85

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: rs10441778; hg19: chr9-137808283;