rs966824

Variant names:

• chr14-61733800-T-C
• rs966824
• NM_001530.4:c.881-338T>C

Variant summary

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

The NM_001530.4(HIF1A):​c.881-338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 152,192 control chromosomes in the GnomAD database, including 60,500 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 0.89 (60500 hom., cov: 32)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 13 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 = 0.957 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.881-338T>C		intron	N/A	NP_001521.1	D0VY79
	HIF1A	NM_001243084.2		c.953-338T>C		intron	N/A	NP_001230013.1	Q16665-3
	HIF1A	NM_181054.3		c.881-338T>C		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.881-338T>C		intron	N/A	ENSP00000338018.4	Q16665-1
	HIF1A	ENST00000539097.2	TSL:1	c.953-338T>C		intron	N/A	ENSP00000437955.1	Q16665-3
	HIF1A	ENST00000394997.5	TSL:1	c.884-338T>C		intron	N/A	ENSP00000378446.1	A8MYV6

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134629 AN: 152074 Hom.: 60472 Cov.: 32

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.936

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.838

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.976

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.901

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

GnomAD4 genome AF: 0.885 AC: 134717 AN: 152192 Hom.: 60500 Cov.: 32 AF XY: 0.885 AC XY: 65853 AN XY: 74414

African (AFR) AF: 0.721 AC: 29921 AN: 41476

American (AMR) AF: 0.936 AC: 14299 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.900 AC: 3124 AN: 3472

East Asian (EAS) AF: 0.839 AC: 4350 AN: 5184

South Asian (SAS) AF: 0.847 AC: 4089 AN: 4828

European-Finnish (FIN) AF: 0.976 AC: 10358 AN: 10612

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65517 AN: 68024

Other (OTH) AF: 0.902 AC: 1903 AN: 2110

Alfa AF: 0.926 Hom.: 34592

Bravo AF: 0.877

Asia WGS AF: 0.847 AC: 2945 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	1.0
DANN	Benign	0.53
PhyloP100		-0.76
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: rs966824; hg19: chr14-62200518;