14-61697832-ATTT-ATTTT

Variant names:

• chr14-61697832-A-AT
• rs113243889
• ENST00000539097:c.-9dupT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_001243084.2(HIF1A):​c.-9dupT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,379,122 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00047 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (1 hom.)
• Consequence: HIF1A NM_001243084.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 71 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 rank	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.35+2003dupT		intron_variant	Intron 1 of 14	ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.-9dupT		5_prime_UTR_variant	Exon 1 of 15		NP_001230013.1
HIF1A	NM_181054.3	c.35+2003dupT		intron_variant	Intron 1 of 13		NP_851397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.35+2003dupT		intron_variant	Intron 1 of 14	1	NM_001530.4	ENSP00000338018.4

Frequencies

GnomAD3 genomes AF: 0.000478 AC: 72 AN: 150588 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000365

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000531

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.00147

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000282

Gnomad OTH AF: 0.000484

GnomAD4 exome AF: 0.00327 AC: 4019 AN: 1228418 Hom.: 1 Cov.: 29 AF XY: 0.00343 AC XY: 2074 AN XY: 603886

Gnomad4 AFR exome AF: 0.00334

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00611

Gnomad4 EAS exome AF: 0.00848

Gnomad4 SAS exome AF: 0.00712

Gnomad4 FIN exome AF: 0.00324

Gnomad4 NFE exome AF: 0.00258

Gnomad4 OTH exome AF: 0.00379

GnomAD4 genome AF: 0.000471 AC: 71 AN: 150704 Hom.: 0 Cov.: 32 AF XY: 0.000543 AC XY: 40 AN XY: 73624

Gnomad4 AFR AF: 0.000364

Gnomad4 AMR AF: 0.000530

Gnomad4 ASJ AF: 0.00203

Gnomad4 EAS AF: 0.00271

Gnomad4 SAS AF: 0.00147

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000282

Gnomad4 OTH AF: 0.000479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs113243889; hg19: chr14-62164550;