rs786205091

Variant names:

• chr13-113118455-GGCGGGTGGCGCAGGTCA-G
• rs786205091
• NM_019616.4:c.783_799delGCGGGTGGCGCAGGTCA

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

The NM_019616.4(F7):​c.783_799delGCGGGTGGCGCAGGTCA​(p.Arg262HisfsTer27) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: F7 NM_019616.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 6.06
• Publications: 0 publications found

Genes affected

F7 (HGNC:3544): (coagulation factor VII) This gene encodes coagulation factor VII which is a vitamin K-dependent factor essential for hemostasis. This factor circulates in the blood in a zymogen form, and is converted to an active form by either factor IXa, factor Xa, factor XIIa, or thrombin by minor proteolysis. Upon activation of the factor VII, a heavy chain containing a catalytic domain and a light chain containing 2 EGF-like domains are generated, and two chains are held together by a disulfide bond. In the presence of factor III and calcium ions, the activated factor then further activates the coagulation cascade by converting factor IX to factor IXa and/or factor X to factor Xa. Defects in this gene can cause coagulopathy. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar proteolytic processing to generate mature polypeptides. [provided by RefSeq, Aug 2015]

F7 Gene-Disease associations (from GenCC):

• congenital factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_pathogenic. The variant received 9 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 40 pathogenic variants in the truncated region.
• PP5: Variant 13-113118455-GGCGGGTGGCGCAGGTCA-G is Pathogenic according to our data. Variant chr13-113118455-GGCGGGTGGCGCAGGTCA-G is described in ClinVar as Pathogenic. ClinVar VariationId is 12077.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019616.4. 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
	F7	NM_019616.4	MANE Select	c.783_799delGCGGGTGGCGCAGGTCA	p.Arg262HisfsTer27	frameshift	Exon 8 of 8	NP_062562.1	P08709-2
	F7	NM_000131.5		c.849_865delGCGGGTGGCGCAGGTCA	p.Arg284HisfsTer27	frameshift	Exon 9 of 9	NP_000122.1
	F7	NM_001267554.2		c.597_613delGCGGGTGGCGCAGGTCA	p.Arg200HisfsTer27	frameshift	Exon 6 of 6	NP_001254483.1	F5H8B0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	ENST00000346342.8	TSL:1 MANE Select	c.783_799delGCGGGTGGCGCAGGTCA	p.Arg262HisfsTer27	frameshift	Exon 8 of 8	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.849_865delGCGGGTGGCGCAGGTCA	p.Arg284HisfsTer27	frameshift	Exon 9 of 9	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.996_1012delGCGGGTGGCGCAGGTCA	p.Arg333HisfsTer27	frameshift	Exon 9 of 9	ENSP00000561314.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Congenital factor VII deficiency (1)
1	-	-	Factor VII deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1
Mutation Taster		=1/199	disease causing (ClinVar)

Splicing

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

Other links and lift over

dbSNP: rs786205091; hg19: chr13-113772769;