Variant chr14-61732540-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBS2_Supporting

The NM_001530.4(HIF1A):c.880+16G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,402,876 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00082 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 2 hom. )

Consequence

HIF1A
NM_001530.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0280

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-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 -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 14-61732540-G-T is Benign according to our data. Variant chr14-61732540-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2920784.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 125 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	Effect	MANE
HIF1A	NM_001530.4 linkuse as main transcript	c.880+16G>T	intron_variant	ENST00000337138.9
HIF1A-AS3	NR_144368.1 linkuse as main transcript	n.214-15523C>A	intron_variant, non_coding_transcript_variant
HIF1A	NM_001243084.2 linkuse as main transcript	c.952+16G>T	intron_variant
HIF1A	NM_181054.3 linkuse as main transcript	c.880+16G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9 linkuse as main transcript	c.880+16G>T		intron_variant		1	NM_001530.4	P4	Q16665-1
HIF1A-AS3	ENST00000660325.2 linkuse as main transcript	n.215+18345C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000822

AC:

125

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00144

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000832

AC:

205

AN:

246248

Hom.:

AF XY:

0.000938

AC XY:

125

AN XY:

133258

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.00121

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.000151

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.000662

GnomAD4 exome

AF:

0.00132

AC:

1651

AN:

1250604

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

817

AN XY:

632860

show subpopulations

Gnomad4 AFR exome

AF:

0.000136

Gnomad4 AMR exome

AF:

0.00127

Gnomad4 ASJ exome

AF:

0.000202

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.000253

Gnomad4 NFE exome

AF:

0.00163

Gnomad4 OTH exome

AF:

0.00109

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152272

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00144

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000854

Hom.:

Bravo

AF:

0.000808

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Apr 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.86

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over