rs1957757

chr14-61730230-T-C

Variant summary

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

The NM_001530.4(HIF1A):c.774-2188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 152,094 control chromosomes in the GnomAD database, including 46,913 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 0.74 (46913 hom., cov: 31)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIF1A	NM_001530.4	c.774-2188T>C		intron_variant		ENST00000337138.9
HIF1A-AS3	NR_144368.1	n.214-13213A>G		intron_variant, non_coding_transcript_variant
HIF1A	NM_001243084.2	c.846-2188T>C		intron_variant
HIF1A	NM_181054.3	c.774-2188T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9	c.774-2188T>C		intron_variant		1	NM_001530.4	P4
HIF1A-AS3	ENST00000660325.2	n.216-16228A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112812 AN: 151976 Hom.: 46894 Cov.: 31

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.964

Gnomad AMR AF: 0.849

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.786

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.742 AC: 112876 AN: 152094 Hom.: 46913 Cov.: 31 AF XY: 0.747 AC XY: 55551 AN XY: 74334

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.849

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.769

Alfa AF: 0.881 Hom.: 78527

Bravo AF: 0.719

Asia WGS AF: 0.800 AC: 2781 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.85
Dann	Benign	0.69

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: rs1957757; hg19: chr14-62196948;