13-113115325-T-G

Position:

• chr13-113115325-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4	c.365-335T>G		intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.365-335T>G		intron_variant		1	NM_019616.4	P2

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

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.0479

Gnomad4 SAS AF: 0.277

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.191

Alfa AF: 0.153 Hom.: 438

Bravo AF: 0.191

Asia WGS AF: 0.174 AC: 605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs493833; hg19: chr13-113769639;