14-61697832-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000539097.2(HIF1A):c.-9del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,402,824 control chromosomes in the GnomAD database, including 174 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (97 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (77 hom.)
• Consequence: HIF1A ENST00000539097.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 14-61697832-AT-A is Benign according to our data. Variant chr14-61697832-AT-A is described in ClinVar as [Benign]. Clinvar id is 2920767.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIF1A	NM_001530.4	c.35+2003del		intron_variant		ENST00000337138.9
HIF1A	NM_001243084.2	c.-9del		5_prime_UTR_variant	1/15
HIF1A	NM_181054.3	c.35+2003del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9	c.35+2003del		intron_variant		1	NM_001530.4	P4

Frequencies

GnomAD3 genomes AF: 0.0186 AC: 2804 AN: 150592 Hom.: 91 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00810

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00579

Gnomad SAS AF: 0.000629

Gnomad FIN AF: 0.00117

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000296

Gnomad OTH AF: 0.0189

GnomAD4 exome AF: 0.00276 AC: 3451 AN: 1252116 Hom.: 77 Cov.: 29 AF XY: 0.00260 AC XY: 1600 AN XY: 615848

Gnomad4 AFR exome AF: 0.0711

Gnomad4 AMR exome AF: 0.00788

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.00552

Gnomad4 SAS exome AF: 0.00208

Gnomad4 FIN exome AF: 0.00167

Gnomad4 NFE exome AF: 0.000565

Gnomad4 OTH exome AF: 0.00723

GnomAD4 genome AF: 0.0188 AC: 2832 AN: 150708 Hom.: 97 Cov.: 32 AF XY: 0.0187 AC XY: 1380 AN XY: 73624

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.00809

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00580

Gnomad4 SAS AF: 0.000630

Gnomad4 FIN AF: 0.00117

Gnomad4 NFE AF: 0.000296

Gnomad4 OTH AF: 0.0187

Alfa AF: 0.00558 Hom.: 0

Bravo AF: 0.0215

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Sep 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113243889; hg19: chr14-62164550;