13-113109612-G-T

Position:

• chr13-113109612-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019616.4(F7):​c.65-1078G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,016 control chromosomes in the GnomAD database, including 6,920 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 0.29 (6920 hom., cov: 33)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F7	NM_019616.4	c.65-1078G>T		intron_variant		ENST00000346342.8	NP_062562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F7	ENST00000346342.8	c.65-1078G>T		intron_variant		1	NM_019616.4	ENSP00000329546.4
F7	ENST00000375581.3	c.131-1078G>T		intron_variant		1		ENSP00000364731.3
F7	ENST00000541084.5	c.64+3707G>T		intron_variant		2		ENSP00000442051.2
F7	ENST00000444337.1	n.65-1092G>T		intron_variant		5		ENSP00000387669.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44193 AN: 151898 Hom.: 6897 Cov.: 33

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.291 AC: 44249 AN: 152016 Hom.: 6920 Cov.: 33 AF XY: 0.292 AC XY: 21677 AN XY: 74280

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.295

Alfa AF: 0.229 Hom.: 5165

Bravo AF: 0.306

Asia WGS AF: 0.328 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.97

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: rs1475931; hg19: chr13-113763926;