rs1951795

chr14-61704708-A-Cchr14-61704708-A-T

Variant summary

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

The NM_001530.4(HIF1A):c.35+8869A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,090 control chromosomes in the GnomAD database, including 36,902 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 0.65 (36902 hom., cov: 33)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• 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	UniProt
HIF1A	NM_001530.4	c.35+8869A>C		intron_variant		ENST00000337138.9
HIF1A	NM_001243084.2	c.104+6754A>C		intron_variant
HIF1A	NM_181054.3	c.35+8869A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9	c.35+8869A>C		intron_variant		1	NM_001530.4	P4

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98142 AN: 151972 Hom.: 36891 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.649

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.646 AC: 98185 AN: 152090 Hom.: 36902 Cov.: 33 AF XY: 0.653 AC XY: 48579 AN XY: 74356

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.674

Gnomad4 EAS AF: 0.780

Gnomad4 SAS AF: 0.676

Gnomad4 FIN AF: 0.918

Gnomad4 NFE AF: 0.814

Gnomad4 OTH AF: 0.653

Alfa AF: 0.763 Hom.: 57282

Bravo AF: 0.617

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.5
Dann	Benign	0.88

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: rs1951795; hg19: chr14-62171426;