13-113115325-T-G

Variant names:

• chr13-113115325-T-G
• rs493833
• NM_019616.4:c.365-335T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019616.4(F7):​c.365-335T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,130 control chromosomes in the GnomAD database, including 3,269 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.18 (3269 hom., cov: 33)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 8 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, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• factor VII deficiency

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

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.365-335T>G		intron	N/A	NP_062562.1	P08709-2
	F7	NM_000131.5		c.431-335T>G		intron	N/A	NP_000122.1
	F7	NM_001267554.2		c.179-335T>G		intron	N/A	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.365-335T>G		intron	N/A	ENSP00000329546.4	P08709-2
	F7	ENST00000375581.3	TSL:1	c.431-335T>G		intron	N/A	ENSP00000364731.3	P08709-1
	F7	ENST00000891255.1		c.577+258T>G		intron	N/A	ENSP00000561314.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27723 AN: 152012 Hom.: 3247 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0478

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.183 AC: 27789 AN: 152130 Hom.: 3269 Cov.: 33 AF XY: 0.182 AC XY: 13515 AN XY: 74400

African (AFR) AF: 0.324 AC: 13448 AN: 41454

American (AMR) AF: 0.150 AC: 2298 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 724 AN: 3472

East Asian (EAS) AF: 0.0479 AC: 248 AN: 5176

South Asian (SAS) AF: 0.277 AC: 1333 AN: 4816

European-Finnish (FIN) AF: 0.0767 AC: 814 AN: 10616

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8293 AN: 67990

Other (OTH) AF: 0.191 AC: 405 AN: 2116

Alfa AF: 0.146 Hom.: 2785

Bravo AF: 0.191

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.28
PhyloP100		-0.64
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs493833;

hg19: chr13-113769639;