rs10873142

Positions:

• chr14-61736744-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001530.4(HIF1A):​c.1029-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 618,868 control chromosomes in the GnomAD database, including 181,797 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.67 (38057 hom., cov: 32)
  • Exomes 𝑓: 0.78 (143740 hom.)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.1029-145C>T		intron_variant		ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.1101-145C>T		intron_variant			NP_001230013.1
HIF1A	NM_181054.3	c.1029-145C>T		intron_variant			NP_851397.1
HIF1A-AS3	NR_144368.1	n.213+14141G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.1029-145C>T		intron_variant		1	NM_001530.4	ENSP00000338018.4

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102428 AN: 152002 Hom.: 38034 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.778 AC: 363143 AN: 466748 Hom.: 143740 AF XY: 0.775 AC XY: 191282 AN XY: 246890

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.781

Gnomad4 ASJ exome AF: 0.674

Gnomad4 EAS exome AF: 0.766

Gnomad4 SAS exome AF: 0.683

Gnomad4 FIN exome AF: 0.909

Gnomad4 NFE exome AF: 0.807

Gnomad4 OTH exome AF: 0.746

GnomAD4 genome AF: 0.674 AC: 102501 AN: 152120 Hom.: 38057 Cov.: 32 AF XY: 0.681 AC XY: 50680 AN XY: 74388

Gnomad4 AFR AF: 0.340

Gnomad4 AMR AF: 0.749

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.765

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.919

Gnomad4 NFE AF: 0.813

Gnomad4 OTH AF: 0.676

Alfa AF: 0.719 Hom.: 6142

Bravo AF: 0.649

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.5
DANN	Benign	0.38

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: rs10873142; hg19: chr14-62203462;