rs10129270

Variant names:

• chr14-61715236-G-A
• rs10129270
• NM_001530.4:c.36-5146G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001530.4(HIF1A):​c.36-5146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,086 control chromosomes in the GnomAD database, including 3,288 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 0.16 (3288 hom., cov: 32)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754
• Publications: 9 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001530.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF1A	NM_001530.4	MANE Select	c.36-5146G>A		intron	N/A	NP_001521.1
	HIF1A	NM_001243084.2		c.105-5143G>A		intron	N/A	NP_001230013.1
	HIF1A	NM_181054.3		c.36-5146G>A		intron	N/A	NP_851397.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF1A	ENST00000337138.9	TSL:1 MANE Select	c.36-5146G>A		intron	N/A	ENSP00000338018.4
	HIF1A	ENST00000539097.2	TSL:1	c.105-5143G>A		intron	N/A	ENSP00000437955.1
	HIF1A	ENST00000394997.5	TSL:1	c.36-5143G>A		intron	N/A	ENSP00000378446.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24013 AN: 151968 Hom.: 3289 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0583

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.158 AC: 24028 AN: 152086 Hom.: 3288 Cov.: 32 AF XY: 0.156 AC XY: 11575 AN XY: 74370

African (AFR) AF: 0.375 AC: 15542 AN: 41420

American (AMR) AF: 0.103 AC: 1576 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 582 AN: 3470

East Asian (EAS) AF: 0.152 AC: 784 AN: 5174

South Asian (SAS) AF: 0.188 AC: 908 AN: 4822

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10600

Middle Eastern (MID) AF: 0.192 AC: 56 AN: 292

European-Non Finnish (NFE) AF: 0.0583 AC: 3966 AN: 68004

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.0990 Hom.: 3689

Bravo AF: 0.170

Asia WGS AF: 0.162 AC: 562 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.74
PhyloP100		-0.75
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: rs10129270; hg19: chr14-62181954;