NM_000130.5:c.1763-260T>C

Variant names:

• chr1-169544768-A-G
• rs1018827
• NM_000130.5:c.1763-260T>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.1763-260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,316 control chromosomes in the GnomAD database, including 64,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.92 (64913 hom., cov: 33)
• Consequence: F5 NM_000130.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.138
• Publications: 23 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=-0.95).
• BP6: Variant 1-169544768-A-G is Benign according to our data. Variant chr1-169544768-A-G is described in ClinVar as Benign. ClinVar VariationId is 1230677.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F5	NM_000130.5	c.1763-260T>C		intron_variant	Intron 11 of 24	ENST00000367797.9	NP_000121.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F5	ENST00000367797.9	c.1763-260T>C		intron_variant	Intron 11 of 24	1	NM_000130.5	ENSP00000356771.3
F5	ENST00000367796.3	c.1763-245T>C		intron_variant	Intron 11 of 24	5		ENSP00000356770.3

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140448 AN: 152198 Hom.: 64861 Cov.: 33

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.946

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.933

Gnomad OTH AF: 0.924

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

GnomAD4 genome AF: 0.923 AC: 140558 AN: 152316 Hom.: 64913 Cov.: 33 AF XY: 0.924 AC XY: 68838 AN XY: 74478

African (AFR) AF: 0.885 AC: 36787 AN: 41560

American (AMR) AF: 0.951 AC: 14555 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.935 AC: 4510 AN: 4824

European-Finnish (FIN) AF: 0.946 AC: 10035 AN: 10612

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.933 AC: 63460 AN: 68042

Other (OTH) AF: 0.925 AC: 1956 AN: 2114

Alfa AF: 0.928 Hom.: 180969

Bravo AF: 0.921

Asia WGS AF: 0.972 AC: 3374 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.6
DANN	Benign	0.64
PhyloP100		-0.14
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: rs1018827; hg19: chr1-169514006;