13-113107199-C-T

Position:

• chr13-113107199-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_019616.4(F7):​c.64+1294C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 150,628 control chromosomes in the GnomAD database, including 4,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4373 hom., cov: 31)
• Consequence: F7 NM_019616.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 13-113107199-C-T is Benign according to our data. Variant chr13-113107199-C-T is described in ClinVar as [Benign]. Clinvar id is 1271772.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F7	NM_019616.4	c.64+1294C>T		intron_variant		ENST00000346342.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F7	ENST00000346342.8	c.64+1294C>T		intron_variant		1	NM_019616.4	P2
F7	ENST00000375581.3	c.130+289C>T		intron_variant		1		A2
F7	ENST00000541084.5	c.64+1294C>T		intron_variant		2
F7	ENST00000444337.1	c.64+1294C>T		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.232 AC: 34931 AN: 150514 Hom.: 4353 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.0740

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.232 AC: 34980 AN: 150628 Hom.: 4373 Cov.: 31 AF XY: 0.236 AC XY: 17341 AN XY: 73566

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0740

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.208

Alfa AF: 0.182 Hom.: 502

Bravo AF: 0.236

Asia WGS AF: 0.280 AC: 945 AN: 3376

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs28663357; hg19: chr13-113761513;