rs34005929
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting
The NM_001530.4(HIF1A):c.1740G>A(p.Leu580=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,614,068 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 11 hom. )
Consequence
HIF1A
NM_001530.4 synonymous
NM_001530.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.117
Genes affected
HIF1A (HGNC:4910): (hypoxia inducible factor 1 subunit alpha) This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
Variant 14-61740835-G-A is Benign according to our data. Variant chr14-61740835-G-A is described in ClinVar as [Benign]. Clinvar id is 716776.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.117 with no splicing effect.
BS2
?
High AC in GnomAd4 at 306 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIF1A | NM_001530.4 | c.1740G>A | p.Leu580= | synonymous_variant | 12/15 | ENST00000337138.9 | |
HIF1A-AS3 | NR_144368.1 | n.213+10050C>T | intron_variant, non_coding_transcript_variant | ||||
HIF1A | NM_001243084.2 | c.1812G>A | p.Leu604= | synonymous_variant | 12/15 | ||
HIF1A | NM_181054.3 | c.1740G>A | p.Leu580= | synonymous_variant | 12/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIF1A | ENST00000337138.9 | c.1740G>A | p.Leu580= | synonymous_variant | 12/15 | 1 | NM_001530.4 | P4 | |
HIF1A-AS3 | ENST00000660325.2 | n.215+10050C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00200 AC: 305AN: 152130Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00241 AC: 607AN: 251472Hom.: 1 AF XY: 0.00249 AC XY: 338AN XY: 135910
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GnomAD4 exome AF: 0.00279 AC: 4084AN: 1461820Hom.: 11 Cov.: 31 AF XY: 0.00286 AC XY: 2080AN XY: 727220
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GnomAD4 genome ? AF: 0.00201 AC: 306AN: 152248Hom.: 2 Cov.: 32 AF XY: 0.00193 AC XY: 144AN XY: 74448
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 23, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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