NM_002003.5:c.128G>A

Variant names:

• chr9-134916437-C-T
• rs10441778
• NM_002003.5:c.128G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 (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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 18 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	NM_002003.5	MANE Select	c.128G>A	p.Gly43Asp	missense	Exon 2 of 9	NP_001994.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	ENST00000371806.4	TSL:1 MANE Select	c.128G>A	p.Gly43Asp	missense	Exon 2 of 9	ENSP00000360871.3	O00602
	FCN1	ENST00000954365.1		c.128G>A	p.Gly43Asp	missense	Exon 2 of 9	ENSP00000624424.1
	FCN1	ENST00000954366.1		c.128G>A	p.Gly43Asp	missense	Exon 2 of 9	ENSP00000624425.1

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

GnomAD2 exomes AF: 0.00298 AC: 749 AN: 251434 AF XY: 0.00213

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 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

African (AFR) AF: 0.0350 AC: 1172 AN: 33478

American (AMR) AF: 0.00380 AC: 170 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53390

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000208 AC: 231 AN: 1112002

Other (OTH) AF: 0.00293 AC: 177 AN: 60394

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

African (AFR) AF: 0.0335 AC: 1394 AN: 41592

American (AMR) AF: 0.00366 AC: 56 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10632

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68034

Other (OTH) AF: 0.00756 AC: 16 AN: 2116

Alfa AF: 0.00497 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 v4.9

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
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0059	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.19
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.36
Sift	Benign	0.12	T
Sift4G	Uncertain	0.019	D
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
Mutation Taster		=97/3	polymorphism

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: rs10441778; hg19: chr9-137808283;