rs10873142

Variant names:

• chr14-61736744-C-T
• rs10873142
• NM_001530.4:c.1029-145C>T

Variant summary

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

The NM_001530.4(HIF1A):​c.1029-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 618,868 control chromosomes in the GnomAD database, including 181,797 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 0.67 (38057 hom., cov: 32)
  • Exomes 𝑓: 0.78 (143740 hom.)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• Publications: 29 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]

ENSG00000258667 (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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF1A	NM_001530.4	MANE Select	c.1029-145C>T		intron	N/A	NP_001521.1	D0VY79
	HIF1A	NM_001243084.2		c.1101-145C>T		intron	N/A	NP_001230013.1	Q16665-3
	HIF1A	NM_181054.3		c.1029-145C>T		intron	N/A	NP_851397.1	Q16665-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF1A	ENST00000337138.9	TSL:1 MANE Select	c.1029-145C>T		intron	N/A	ENSP00000338018.4	Q16665-1
	HIF1A	ENST00000539097.2	TSL:1	c.1101-145C>T		intron	N/A	ENSP00000437955.1	Q16665-3
	HIF1A	ENST00000394997.5	TSL:1	c.1032-145C>T		intron	N/A	ENSP00000378446.1	A8MYV6

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102428 AN: 152002 Hom.: 38034 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.835

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.919

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.673

GnomAD4 exome AF: 0.778 AC: 363143 AN: 466748 Hom.: 143740 AF XY: 0.775 AC XY: 191282 AN XY: 246890

African (AFR) AF: 0.345 AC: 4396 AN: 12756

American (AMR) AF: 0.781 AC: 15301 AN: 19598

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 9495 AN: 14092

East Asian (EAS) AF: 0.766 AC: 24067 AN: 31408

South Asian (SAS) AF: 0.683 AC: 31309 AN: 45834

European-Finnish (FIN) AF: 0.909 AC: 31954 AN: 35150

Middle Eastern (MID) AF: 0.645 AC: 1301 AN: 2016

European-Non Finnish (NFE) AF: 0.807 AC: 225437 AN: 279234

Other (OTH) AF: 0.746 AC: 19883 AN: 26660

GnomAD4 genome AF: 0.674 AC: 102501 AN: 152120 Hom.: 38057 Cov.: 32 AF XY: 0.681 AC XY: 50680 AN XY: 74388

African (AFR) AF: 0.340 AC: 14098 AN: 41440

American (AMR) AF: 0.749 AC: 11459 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2319 AN: 3472

East Asian (EAS) AF: 0.765 AC: 3958 AN: 5174

South Asian (SAS) AF: 0.675 AC: 3255 AN: 4824

European-Finnish (FIN) AF: 0.919 AC: 9741 AN: 10602

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55303 AN: 67996

Other (OTH) AF: 0.676 AC: 1430 AN: 2114

Alfa AF: 0.719 Hom.: 6142

Bravo AF: 0.649

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.5
DANN	Benign	0.38
PhyloP100		0.32
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: rs10873142; hg19: chr14-62203462;