14-61732236-G-C

Variant names:

• chr14-61732236-G-C
• rs11158358
• NM_001530.4:c.774-182G>C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.774-182G>C		intron_variant	Intron 6 of 14	ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.846-182G>C		intron_variant	Intron 6 of 14		NP_001230013.1
HIF1A	NM_181054.3	c.774-182G>C		intron_variant	Intron 6 of 13		NP_851397.1
HIF1A-AS3	NR_144368.1	n.214-15219C>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.774-182G>C		intron_variant	Intron 6 of 14	1	NM_001530.4	ENSP00000338018.4

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

Gnomad4 AFR AF: 0.660

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.719

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.835

Gnomad4 OTH AF: 0.775

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.23
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs11158358; hg19: chr14-62198954;