chr9-134918015-G-T

Variant names:

• chr9-134918015-G-T
• rs10117466
• NM_002003.5:c.-144C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0310
• Publications: 29 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 -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 VariationId 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.

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.-144C>A		upstream_gene	N/A	NP_001994.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN1	ENST00000371806.4	TSL:1 MANE Select	c.-144C>A		upstream_gene	N/A	ENSP00000360871.3	O00602
	FCN1	ENST00000954365.1		c.-144C>A		upstream_gene	N/A	ENSP00000624424.1
	FCN1	ENST00000954366.1		c.-144C>A		upstream_gene	N/A	ENSP00000624425.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37977 AN: 151954 Hom.: 5431 Cov.: 32

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

African (AFR) AF: 0.136 AC: 1666 AN: 12284

American (AMR) AF: 0.171 AC: 3418 AN: 19964

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 3163 AN: 13336

East Asian (EAS) AF: 0.00246 AC: 73 AN: 29708

South Asian (SAS) AF: 0.199 AC: 8885 AN: 44728

European-Finnish (FIN) AF: 0.313 AC: 8965 AN: 28668

Middle Eastern (MID) AF: 0.283 AC: 592 AN: 2094

European-Non Finnish (NFE) AF: 0.323 AC: 83734 AN: 259226

Other (OTH) AF: 0.265 AC: 6613 AN: 24998

GnomAD4 genome AF: 0.250 AC: 37968 AN: 152072 Hom.: 5430 Cov.: 32 AF XY: 0.247 AC XY: 18327 AN XY: 74342

African (AFR) AF: 0.137 AC: 5700 AN: 41504

American (AMR) AF: 0.215 AC: 3284 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 862 AN: 3466

East Asian (EAS) AF: 0.00792 AC: 41 AN: 5180

South Asian (SAS) AF: 0.181 AC: 870 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3637 AN: 10566

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22513 AN: 67950

Other (OTH) AF: 0.248 AC: 523 AN: 2108

Alfa AF: 0.280 Hom.: 3598

Bravo AF: 0.235

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.37
PhyloP100		-0.031
PromoterAI		0.23	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10117466; hg19: chr9-137809861;