rs5742910

Variant names:

• chr13-113105516-T-TTCCTATATCC
• rs5742910
• ENST00000891240.1:c.-326_-325insTCCTATATCC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000891240.1(F7):​c.-326_-325insTCCTATATCC variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,174 control chromosomes in the GnomAD database, including 2,907 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2907 hom., cov: 28)
• Consequence: F7 ENST00000891240.1 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: -0.243
• Publications: 21 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 -10 ACMG points.

• BP6: Variant 13-113105516-T-TTCCTATATCC is Benign according to our data. Variant chr13-113105516-T-TTCCTATATCC is described in ClinVar as Benign. ClinVar VariationId is 12079.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000891240.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F7	ENST00000891240.1		c.-326_-325insTCCTATATCC		upstream_gene	N/A	ENSP00000561299.1
	F7	ENST00000891239.1		c.-326_-325insTCCTATATCC		upstream_gene	N/A	ENSP00000561298.1

Frequencies

GnomAD3 genomes AF: 0.175 AC: 26632 AN: 152056 Hom.: 2899 Cov.: 28

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0397

Gnomad SAS AF: 0.271

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.175 AC: 26673 AN: 152174 Hom.: 2907 Cov.: 28 AF XY: 0.174 AC XY: 12964 AN XY: 74422

African (AFR) AF: 0.304 AC: 12596 AN: 41466

American (AMR) AF: 0.144 AC: 2200 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 669 AN: 3472

East Asian (EAS) AF: 0.0398 AC: 206 AN: 5182

South Asian (SAS) AF: 0.272 AC: 1311 AN: 4820

European-Finnish (FIN) AF: 0.0759 AC: 806 AN: 10622

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8276 AN: 67992

Other (OTH) AF: 0.180 AC: 380 AN: 2112

Alfa AF: 0.0523 Hom.: 54

Asia WGS AF: 0.164 AC: 571 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	-	Myocardial infarction, decreased susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24

Splicing

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: rs5742910;

hg19: chr13-113759830;