rs966824

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001530.4(HIF1A):​c.881-338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,192 control chromosomes in the GnomAD database, including 60,500 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.89 ( 60500 hom., cov: 32)

Consequence

HIF1A
NM_001530.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.761
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.95).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
HIF1ANM_001530.4 linkuse as main transcriptc.881-338T>C intron_variant ENST00000337138.9
HIF1A-AS3NR_144368.1 linkuse as main transcriptn.214-16783A>G intron_variant, non_coding_transcript_variant
HIF1ANM_001243084.2 linkuse as main transcriptc.953-338T>C intron_variant
HIF1ANM_181054.3 linkuse as main transcriptc.881-338T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIF1AENST00000337138.9 linkuse as main transcriptc.881-338T>C intron_variant 1 NM_001530.4 P4Q16665-1
HIF1A-AS3ENST00000660325.2 linkuse as main transcriptn.215+17085A>G intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.885
AC:
134629
AN:
152074
Hom.:
60472
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.722
Gnomad AMI
AF:
0.978
Gnomad AMR
AF:
0.936
Gnomad ASJ
AF:
0.900
Gnomad EAS
AF:
0.838
Gnomad SAS
AF:
0.847
Gnomad FIN
AF:
0.976
Gnomad MID
AF:
0.899
Gnomad NFE
AF:
0.963
Gnomad OTH
AF:
0.901
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.885
AC:
134717
AN:
152192
Hom.:
60500
Cov.:
32
AF XY:
0.885
AC XY:
65853
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.721
Gnomad4 AMR
AF:
0.936
Gnomad4 ASJ
AF:
0.900
Gnomad4 EAS
AF:
0.839
Gnomad4 SAS
AF:
0.847
Gnomad4 FIN
AF:
0.976
Gnomad4 NFE
AF:
0.963
Gnomad4 OTH
AF:
0.902
Alfa
AF:
0.926
Hom.:
30856
Bravo
AF:
0.877
Asia WGS
AF:
0.847
AC:
2945
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.95
CADD
Benign
1.0
DANN
Benign
0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs966824; hg19: chr14-62200518; API