GeneBe

13-113105720-T-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_019616.4(F7):​c.-122T>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

F7
NM_019616.4 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

48 publications found
Variant links:
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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Orphanet, Ambry Genetics
  • factor VII deficiency
    Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
F7NM_019616.4 linkc.-122T>G upstream_gene_variant ENST00000346342.8 NP_062562.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
F7ENST00000346342.8 linkc.-122T>G upstream_gene_variant 1 NM_019616.4 ENSP00000329546.4
F7ENST00000375581.3 linkc.-122T>G upstream_gene_variant 1 ENSP00000364731.3
F7ENST00000541084.5 linkc.-122T>G upstream_gene_variant 2 ENSP00000442051.2
F7ENST00000444337.1 linkn.-122T>G upstream_gene_variant 5 ENSP00000387669.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
994352
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
503394
African (AFR)
AF:
0.00
AC:
0
AN:
23896
American (AMR)
AF:
0.00
AC:
0
AN:
35068
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22742
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33666
South Asian (SAS)
AF:
0.00
AC:
0
AN:
71144
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
35552
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4828
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
722680
Other (OTH)
AF:
0.00
AC:
0
AN:
44776
GnomAD4 genome
Cov.:
31
Alfa
AF:
0.00
Hom.:
690

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.75
CADD
Benign
2.4
DANN
Benign
0.87
PhyloP100
-1.1
PromoterAI
-0.0094
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs561241; hg19: chr13-113760034; API