rs8005745

Positions:

• chr14-61718577-T-A
• chr14-61718577-T-C
• chr14-61718577-T-G

Variant summary

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

The NM_001530.4(HIF1A):​c.36-1805T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,118 control chromosomes in the GnomAD database, including 46,692 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 0.75 (46692 hom., cov: 31)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.36-1805T>A		intron_variant		ENST00000337138.9	NP_001521.1
HIF1A-AS3	NR_144368.1	n.214-1560A>T		intron_variant, non_coding_transcript_variant
HIF1A	NM_001243084.2	c.105-1802T>A		intron_variant			NP_001230013.1
HIF1A	NM_181054.3	c.36-1805T>A		intron_variant			NP_851397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.36-1805T>A		intron_variant		1	NM_001530.4	ENSP00000338018	P4
HIF1A-AS3	ENST00000660325.2	n.216-4575A>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113593 AN: 151998 Hom.: 46668 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.939

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.907

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.747 AC: 113668 AN: 152118 Hom.: 46692 Cov.: 31 AF XY: 0.753 AC XY: 56001 AN XY: 74386

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.907

Gnomad4 OTH AF: 0.764

Alfa AF: 0.875 Hom.: 28818

Bravo AF: 0.726

Asia WGS AF: 0.797 AC: 2772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.51

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: rs8005745; hg19: chr14-62185295;