chr14-61727515-G-A
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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.633G>A(p.Gly211=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000417 in 1,613,822 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0021 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00024 ( 1 hom. )
Consequence
HIF1A
NM_001530.4 synonymous
NM_001530.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.74
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=-0.79).
BP6
Variant 14-61727515-G-A is Benign according to our data. Variant chr14-61727515-G-A is described in ClinVar as [Benign]. Clinvar id is 731117.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-3.74 with no splicing effect.
BS2
High AC in GnomAd4 at 325 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.633G>A | p.Gly211= | synonymous_variant | 6/15 | ENST00000337138.9 | |
HIF1A-AS3 | NR_144368.1 | n.214-10498C>T | intron_variant, non_coding_transcript_variant | ||||
HIF1A | NM_001243084.2 | c.705G>A | p.Gly235= | synonymous_variant | 6/15 | ||
HIF1A | NM_181054.3 | c.633G>A | p.Gly211= | synonymous_variant | 6/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIF1A | ENST00000337138.9 | c.633G>A | p.Gly211= | synonymous_variant | 6/15 | 1 | NM_001530.4 | P4 | |
HIF1A-AS3 | ENST00000660325.2 | n.216-13513C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00214 AC: 325AN: 152016Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000601 AC: 151AN: 251396Hom.: 1 AF XY: 0.000420 AC XY: 57AN XY: 135868
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GnomAD4 exome AF: 0.000238 AC: 348AN: 1461688Hom.: 1 Cov.: 31 AF XY: 0.000204 AC XY: 148AN XY: 727170
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GnomAD4 genome AF: 0.00214 AC: 325AN: 152134Hom.: 2 Cov.: 32 AF XY: 0.00216 AC XY: 161AN XY: 74370
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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 | Labcorp Genetics (formerly Invitae), Labcorp | Apr 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at