Variant 14-61747130-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000337138.9(HIF1A):c.*45T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.844 in 1,548,668 control chromosomes in the GnomAD database, including 554,863 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 0.80 ( 49554 hom., cov: 32)

Exomes 𝑓: 0.85 ( 505309 hom. )

Consequence

HIF1A
ENST00000337138.9 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.54

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 links:

HIF1A-AS2 (HGNC:):

HIF1A-AS2 links:

HIF1A-AS3 (HGNC:54284): (HIF1A antisense RNA 3)

HIF1A-AS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
HIF1A	NM_001530.4 linkuse as main transcript	c.*45T>C	3_prime_UTR_variant	15/15	ENST00000337138.9	NP_001521.1
HIF1A-AS2	NR_045406.1 linkuse as main transcript	n.1960A>G	non_coding_transcript_exon_variant	1/1
HIF1A-AS3	NR_144368.1 linkuse as main transcript	n.213+3755A>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9 linkuse as main transcript	c.*45T>C		3_prime_UTR_variant	15/15	1	NM_001530.4	ENSP00000338018	P4	Q16665-1
HIF1A-AS3	ENST00000660325.2 linkuse as main transcript	n.215+3755A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.802

AC:

121899

AN:

152030

Hom.:

49532

Cov.:

show subpopulations

Gnomad AFR

AF:

0.665

Gnomad AMI

AF:

0.848

Gnomad AMR

AF:

0.848

Gnomad ASJ

AF:

0.750

Gnomad EAS

AF:

0.806

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.940

Gnomad MID

AF:

0.731

Gnomad NFE

AF:

0.860

Gnomad OTH

AF:

0.800

GnomAD3 exomes

AF:

0.835

AC:

177949

AN:

213048

Hom.:

74951

AF XY:

0.832

AC XY:

95622

AN XY:

114938

show subpopulations

Gnomad AFR exome

AF:

0.663

Gnomad AMR exome

AF:

0.902

Gnomad ASJ exome

AF:

0.756

Gnomad EAS exome

AF:

0.805

Gnomad SAS exome

AF:

0.743

Gnomad FIN exome

AF:

0.933

Gnomad NFE exome

AF:

0.856

Gnomad OTH exome

AF:

0.838

GnomAD4 exome

AF:

0.849

AC:

1185326

AN:

1396518

Hom.:

505309

Cov.:

AF XY:

0.846

AC XY:

587767

AN XY:

694830

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.894

Gnomad4 ASJ exome

AF:

0.757

Gnomad4 EAS exome

AF:

0.809

Gnomad4 SAS exome

AF:

0.745

Gnomad4 FIN exome

AF:

0.933

Gnomad4 NFE exome

AF:

0.862

Gnomad4 OTH exome

AF:

0.823

GnomAD4 genome

AF:

0.802

AC:

121974

AN:

152150

Hom.:

49554

Cov.:

AF XY:

0.804

AC XY:

59798

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.849

Gnomad4 ASJ

AF:

0.750

Gnomad4 EAS

AF:

0.807

Gnomad4 SAS

AF:

0.733

Gnomad4 FIN

AF:

0.940

Gnomad4 NFE

AF:

0.860

Gnomad4 OTH

AF:

0.802

Alfa

AF:

0.838

Hom.:

96492

Bravo

AF:

0.790

Asia WGS

AF:

0.778

AC:

2706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

0.97

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over