chr14-61736905-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001530.4(HIF1A):c.1045G>A(p.Asp349Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000618 in 1,612,826 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00057 ( 18 hom. )
Consequence
HIF1A
NM_001530.4 missense
NM_001530.4 missense
Scores
1
7
10
Clinical Significance
Conservation
PhyloP100: 6.96
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0066993237).
BP6
?
Variant 14-61736905-G-A is Benign according to our data. Variant chr14-61736905-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 716592.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00108 (165/152250) while in subpopulation EAS AF= 0.0247 (128/5184). AF 95% confidence interval is 0.0212. There are 0 homozygotes in gnomad4. There are 87 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd at 164 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HIF1A | NM_001530.4 | c.1045G>A | p.Asp349Asn | missense_variant | 9/15 | ENST00000337138.9 | |
HIF1A-AS3 | NR_144368.1 | n.213+13980C>T | intron_variant, non_coding_transcript_variant | ||||
HIF1A | NM_001243084.2 | c.1117G>A | p.Asp373Asn | missense_variant | 9/15 | ||
HIF1A | NM_181054.3 | c.1045G>A | p.Asp349Asn | missense_variant | 9/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HIF1A | ENST00000337138.9 | c.1045G>A | p.Asp349Asn | missense_variant | 9/15 | 1 | NM_001530.4 | P4 | |
HIF1A-AS3 | ENST00000660325.2 | n.215+13980C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00108 AC: 164AN: 152132Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00219 AC: 549AN: 251182Hom.: 11 AF XY: 0.00208 AC XY: 282AN XY: 135796
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GnomAD4 exome AF: 0.000570 AC: 832AN: 1460576Hom.: 18 Cov.: 31 AF XY: 0.000564 AC XY: 410AN XY: 726712
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 01, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jul 29, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Benign
D;D;D;T;D
Sift4G
Benign
T;T;T;T;T
Polyphen
P;P;.;.;.
Vest4
MVP
MPC
0.76
ClinPred
T
GERP RS
Varity_R
gMVP
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