Genetic Variant NM_002003.5:c.-144C>A (chr9-134918015-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002003.5(FCN1):c.-144C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 587,078 control chromosomes in the GnomAD database, including 23,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5430 hom., cov: 32)

Exomes 𝑓: 0.27 ( 17785 hom. )

Consequence

FCN1
NM_002003.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0310

Variant links:

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]

FCN1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 9-134918015-G-T is Benign according to our data. Variant chr9-134918015-G-T is described in ClinVar as [Benign]. Clinvar id is 1252732.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN1	NM_002003.5 link	c.-144C>A		upstream_gene_variant		ENST00000371806.4	NP_001994.2	O00602

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN1	ENST00000371806.4 link	c.-144C>A		upstream_gene_variant		1	NM_002003.5	ENSP00000360871.3		O00602

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

37977

AN:

151954

Hom.:

5431

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.00809

Gnomad SAS

AF:

0.181

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.269

AC:

117109

AN:

435006

Hom.:

17785

AF XY:

0.266

AC XY:

61001

AN XY:

229092

show subpopulations

Gnomad4 AFR exome

AF:

0.136

Gnomad4 AMR exome

AF:

0.171

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.00246

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.313

Gnomad4 NFE exome

AF:

0.323

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.250

AC:

37968

AN:

152072

Hom.:

5430

Cov.:

AF XY:

0.247

AC XY:

18327

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.249

Gnomad4 EAS

AF:

0.00792

Gnomad4 SAS

AF:

0.181

Gnomad4 FIN

AF:

0.344

Gnomad4 NFE

AF:

0.331

Gnomad4 OTH

AF:

0.248

Alfa

AF:

0.288

Hom.:

2137

Bravo

AF:

0.235

Asia WGS

AF:

0.100

AC:

347

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 22673311, 23209787) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

DANN

Benign

0.37

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over