chr14-61732415-C-T

Variant summary

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

The NM_001530.4(HIF1A):​c.774-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,578,296 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0017 ( 3 hom. )

Consequence

HIF1A
NM_001530.4 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.001945
2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.12
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 -7 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 14-61732415-C-T is Benign according to our data. Variant chr14-61732415-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2920760.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 187 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.774-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000337138.9
HIF1A-AS3NR_144368.1 linkuse as main transcriptn.214-15398G>A intron_variant, non_coding_transcript_variant
HIF1ANM_001243084.2 linkuse as main transcriptc.846-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
HIF1ANM_181054.3 linkuse as main transcriptc.774-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
HIF1AENST00000337138.9 linkuse as main transcriptc.774-3C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 1 NM_001530.4 P4Q16665-1
HIF1A-AS3ENST00000660325.2 linkuse as main transcriptn.216-18413G>A intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes
AF:
0.00123
AC:
187
AN:
151954
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000508
Gnomad AMI
AF:
0.00548
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00142
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00175
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.00134
AC:
328
AN:
244848
Hom.:
1
AF XY:
0.00140
AC XY:
185
AN XY:
132188
show subpopulations
Gnomad AFR exome
AF:
0.000372
Gnomad AMR exome
AF:
0.000484
Gnomad ASJ exome
AF:
0.000102
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000840
Gnomad NFE exome
AF:
0.00252
Gnomad OTH exome
AF:
0.000837
GnomAD4 exome
AF:
0.00175
AC:
2491
AN:
1426224
Hom.:
3
Cov.:
25
AF XY:
0.00171
AC XY:
1217
AN XY:
711220
show subpopulations
Gnomad4 AFR exome
AF:
0.000185
Gnomad4 AMR exome
AF:
0.000486
Gnomad4 ASJ exome
AF:
0.0000389
Gnomad4 EAS exome
AF:
0.0000254
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00115
Gnomad4 NFE exome
AF:
0.00216
Gnomad4 OTH exome
AF:
0.00107
GnomAD4 genome
AF:
0.00123
AC:
187
AN:
152072
Hom.:
0
Cov.:
32
AF XY:
0.00143
AC XY:
106
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.000506
Gnomad4 AMR
AF:
0.00151
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00142
Gnomad4 NFE
AF:
0.00175
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00130
Hom.:
0
Bravo
AF:
0.00108

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 submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 22, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.58
CADD
Benign
15
DANN
Benign
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.0019
dbscSNV1_RF
Benign
0.14
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: rs200037213; hg19: chr14-62199133; API