14-61732236-G-C

Variant names:

• chr14-61732236-G-C
• rs11158358
• NM_001530.4:c.774-182G>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.774-182G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 152,200 control chromosomes in the GnomAD database, including 47,339 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 0.78 (47339 hom., cov: 33)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.39
• Publications: 14 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.829 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.774-182G>C		intron	N/A	NP_001521.1
	HIF1A	NM_001243084.2		c.846-182G>C		intron	N/A	NP_001230013.1
	HIF1A	NM_181054.3		c.774-182G>C		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.774-182G>C		intron	N/A	ENSP00000338018.4
	HIF1A	ENST00000539097.2	TSL:1	c.846-182G>C		intron	N/A	ENSP00000437955.1
	HIF1A	ENST00000394997.5	TSL:1	c.777-182G>C		intron	N/A	ENSP00000378446.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119189 AN: 152082 Hom.: 47316 Cov.: 33

Gnomad AFR AF: 0.661

Gnomad AMI AF: 0.836

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.783

Gnomad SAS AF: 0.720

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.835

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.784 AC: 119268 AN: 152200 Hom.: 47339 Cov.: 33 AF XY: 0.787 AC XY: 58533 AN XY: 74416

African (AFR) AF: 0.660 AC: 27412 AN: 41512

American (AMR) AF: 0.825 AC: 12603 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2459 AN: 3470

East Asian (EAS) AF: 0.784 AC: 4064 AN: 5182

South Asian (SAS) AF: 0.719 AC: 3465 AN: 4818

European-Finnish (FIN) AF: 0.929 AC: 9862 AN: 10610

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.835 AC: 56797 AN: 68014

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.813 Hom.: 5973

Bravo AF: 0.771

Asia WGS AF: 0.761 AC: 2646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.69
PhyloP100		-2.4
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: rs11158358; hg19: chr14-62198954;