GeneBe

rs41508050

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001530.4(HIF1A):​c.1253C>A​(p.Thr418Lys) variant causes a missense 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. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T418I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Consequence

HIF1A
NM_001530.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.51

Publications

33 publications found
Variant links:
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]
HIF1A-AS3 (HGNC:54284): (HIF1A antisense RNA 3)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.16653273).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HIF1ANM_001530.4 linkc.1253C>A p.Thr418Lys missense_variant Exon 10 of 15 ENST00000337138.9 NP_001521.1
HIF1ANM_001243084.2 linkc.1325C>A p.Thr442Lys missense_variant Exon 10 of 15 NP_001230013.1
HIF1ANM_181054.3 linkc.1253C>A p.Thr418Lys missense_variant Exon 10 of 14 NP_851397.1
HIF1A-AS3NR_144368.1 linkn.213+12795G>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HIF1AENST00000337138.9 linkc.1253C>A p.Thr418Lys missense_variant Exon 10 of 15 1 NM_001530.4 ENSP00000338018.4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.00
Hom.:
11

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.093
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
23
DANN
Benign
0.97
DEOGEN2
Benign
0.36
T;T;.;T;.
Eigen
Benign
-0.069
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.79
T;T;T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.17
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;.;L;.;.
PhyloP100
2.5
PrimateAI
Benign
0.42
T
PROVEAN
Benign
-0.52
N;N;N;N;N
REVEL
Benign
0.040
Sift
Benign
0.035
D;D;D;D;D
Sift4G
Benign
0.91
T;T;T;T;T
Polyphen
0.019
B;B;.;.;.
Vest4
0.31
MutPred
0.38
.;Gain of ubiquitination at T419 (P = 0.0018);.;.;.;
MVP
0.54
MPC
1.0
ClinPred
0.42
T
GERP RS
5.6
Varity_R
0.059
gMVP
0.29
Mutation Taster
=90/10
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs41508050; hg19: chr14-62204808; API