chr13-113106888-G-A
Variant names:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_000131.4(F7):c.108G>A(p.Pro36Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00197 in 1,606,486 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 26 hom. )
Consequence
F7
NM_000131.4 synonymous
NM_000131.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.340
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BP6
Variant 13-113106888-G-A is Benign according to our data. Variant chr13-113106888-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 311220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.34 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1528/152124) while in subpopulation AFR AF= 0.0341 (1414/41468). AF 95% confidence interval is 0.0326. There are 36 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 36 AR gene
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| F7 | ENST00000375581.3 | c.108G>A | p.Pro36Pro | synonymous_variant | Exon 2 of 9 | 1 | ENSP00000364731.3 | |||
| F7 | ENST00000346342.8 | c.64+983G>A | intron_variant | Intron 1 of 7 | 1 | NM_019616.4 | ENSP00000329546.4 | |||
| F7 | ENST00000541084.5 | c.64+983G>A | intron_variant | Intron 1 of 5 | 2 | ENSP00000442051.2 | ||||
| F7 | ENST00000444337.1 | n.64+983G>A | intron_variant | Intron 1 of 4 | 5 | ENSP00000387669.1 |
Frequencies
GnomAD3 genomes 0.0100 AC: 1523AN: 152006Hom.: 36 Cov.: 32
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GnomAD3 exomes AF: 0.00288 AC: 682AN: 236836Hom.: 16 AF XY: 0.00203 AC XY: 261AN XY: 128734
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GnomAD4 exome AF: 0.00112 AC: 1633AN: 1454362Hom.: 26 Cov.: 31 AF XY: 0.00100 AC XY: 726AN XY: 722818
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GnomAD4 genome 0.0100 AC: 1528AN: 152124Hom.: 36 Cov.: 32 AF XY: 0.00965 AC XY: 718AN XY: 74370
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Mar 02, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
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Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided
- -
Factor VII deficiency Benign:1
Apr 27, 2017
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at