rs8005745

Variant names:

• chr14-61718577-T-A
• rs8005745
• NM_001530.4:c.36-1805T>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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:):

HIF1A-AS3 (HGNC:54284): (HIF1A antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.36-1805T>A		intron_variant	Intron 1 of 14	ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.105-1802T>A		intron_variant	Intron 1 of 14		NP_001230013.1
HIF1A	NM_181054.3	c.36-1805T>A		intron_variant	Intron 1 of 13		NP_851397.1
HIF1A-AS3	NR_144368.1	n.214-1560A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.36-1805T>A		intron_variant	Intron 1 of 14	1	NM_001530.4	ENSP00000338018.4

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

African (AFR) AF: 0.373 AC: 15436 AN: 41418

American (AMR) AF: 0.842 AC: 12880 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2785 AN: 3470

East Asian (EAS) AF: 0.833 AC: 4318 AN: 5182

South Asian (SAS) AF: 0.774 AC: 3736 AN: 4826

European-Finnish (FIN) AF: 0.956 AC: 10124 AN: 10594

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.907 AC: 61693 AN: 68010

Other (OTH) AF: 0.764 AC: 1616 AN: 2114

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
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8005745; hg19: chr14-62185295;