rs34005929

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBP6_ModerateBP7BS2_Supporting

The NM_001530.4(HIF1A):​c.1740G>A​(p.Leu580=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,614,068 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 11 hom. )

Consequence

HIF1A
NM_001530.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.117
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 -8 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 14-61740835-G-A is Benign according to our data. Variant chr14-61740835-G-A is described in ClinVar as [Benign]. Clinvar id is 716776.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.117 with no splicing effect.
BS2
High AC in GnomAd4 at 306 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 HGVSp Effect #exon/exons MANE UniProt
HIF1ANM_001530.4 linkuse as main transcriptc.1740G>A p.Leu580= synonymous_variant 12/15 ENST00000337138.9
HIF1A-AS3NR_144368.1 linkuse as main transcriptn.213+10050C>T intron_variant, non_coding_transcript_variant
HIF1ANM_001243084.2 linkuse as main transcriptc.1812G>A p.Leu604= synonymous_variant 12/15
HIF1ANM_181054.3 linkuse as main transcriptc.1740G>A p.Leu580= synonymous_variant 12/14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIF1AENST00000337138.9 linkuse as main transcriptc.1740G>A p.Leu580= synonymous_variant 12/151 NM_001530.4 P4Q16665-1
HIF1A-AS3ENST00000660325.2 linkuse as main transcriptn.215+10050C>T intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00200
AC:
305
AN:
152130
Hom.:
2
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00269
Gnomad FIN
AF:
0.000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00354
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00241
AC:
607
AN:
251472
Hom.:
1
AF XY:
0.00249
AC XY:
338
AN XY:
135910
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000636
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00287
Gnomad FIN exome
AF:
0.00222
Gnomad NFE exome
AF:
0.00380
Gnomad OTH exome
AF:
0.00261
GnomAD4 exome
AF:
0.00279
AC:
4084
AN:
1461820
Hom.:
11
Cov.:
31
AF XY:
0.00286
AC XY:
2080
AN XY:
727220
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000783
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00319
Gnomad4 FIN exome
AF:
0.00253
Gnomad4 NFE exome
AF:
0.00314
Gnomad4 OTH exome
AF:
0.00230
GnomAD4 genome
AF:
0.00201
AC:
306
AN:
152248
Hom.:
2
Cov.:
32
AF XY:
0.00193
AC XY:
144
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00290
Gnomad4 FIN
AF:
0.000944
Gnomad4 NFE
AF:
0.00354
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00265
Hom.:
0
Bravo
AF:
0.00175
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.00382
EpiControl
AF:
0.00279

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJul 23, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
CADD
Benign
6.9
DANN
Benign
0.84

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs34005929; hg19: chr14-62207553; API