1-169558837-C-G

Variant names:

• chr1-169558837-C-G
• rs9332570
• NM_000130.5:c.730+316G>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000130.5(F5):​c.730+316G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,906 control chromosomes in the GnomAD database, including 13,538 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.35 (13538 hom., cov: 31)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.229
• Publications: 6 publications found

Genes affected

F5 (HGNC:3542): (coagulation factor V) This gene encodes an essential cofactor of the blood coagulation cascade. This factor circulates in plasma, and is converted to the active form by the release of the activation peptide by thrombin during coagulation. This generates a heavy chain and a light chain which are held together by calcium ions. The activated protein is a cofactor that participates with activated coagulation factor X to activate prothrombin to thrombin. Defects in this gene result in either an autosomal recessive hemorrhagic diathesis or an autosomal dominant form of thrombophilia, which is known as activated protein C resistance. [provided by RefSeq, Oct 2008]

F5 Gene-Disease associations (from GenCC):

• thrombophilia due to activated protein C resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
• congenital factor V deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)
• East Texas bleeding disorder

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 1-169558837-C-G is Benign according to our data. Variant chr1-169558837-C-G is described in ClinVar as Benign. ClinVar VariationId is 1252982.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.730+316G>C		intron_variant	Intron 5 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.730+316G>C		intron_variant	Intron 5 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.730+316G>C		intron_variant	Intron 5 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53819 AN: 151788 Hom.: 13499 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.0877

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.325

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 53912 AN: 151906 Hom.: 13538 Cov.: 31 AF XY: 0.356 AC XY: 26447 AN XY: 74236

African (AFR) AF: 0.691 AC: 28619 AN: 41420

American (AMR) AF: 0.309 AC: 4716 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3470

East Asian (EAS) AF: 0.653 AC: 3354 AN: 5138

South Asian (SAS) AF: 0.194 AC: 937 AN: 4820

European-Finnish (FIN) AF: 0.256 AC: 2705 AN: 10552

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12028 AN: 67918

Other (OTH) AF: 0.331 AC: 699 AN: 2110

Alfa AF: 0.132 Hom.: 248

Bravo AF: 0.377

Asia WGS AF: 0.458 AC: 1594 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.85
DANN	Benign	0.41
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs9332570; hg19: chr1-169528075;