14-61722813-T-C

Position:

• chr14-61722813-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001530.4(HIF1A):​c.457+990T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,220 control chromosomes in the GnomAD database, including 44,698 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 0.71 (44698 hom., cov: 33)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.457+990T>C		intron_variant		ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.529+990T>C		intron_variant			NP_001230013.1
HIF1A	NM_181054.3	c.457+990T>C		intron_variant			NP_851397.1
HIF1A-AS3	NR_144368.1	n.214-5796A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.457+990T>C		intron_variant		1	NM_001530.4	ENSP00000338018.4

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108576 AN: 152102 Hom.: 44694 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.828

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.902

Gnomad OTH AF: 0.736

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

GnomAD4 genome AF: 0.714 AC: 108609 AN: 152220 Hom.: 44698 Cov.: 33 AF XY: 0.720 AC XY: 53551 AN XY: 74418

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.828

Gnomad4 ASJ AF: 0.799

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.773

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.902

Gnomad4 OTH AF: 0.738

Alfa AF: 0.863 Hom.: 65655

Bravo AF: 0.688

Asia WGS AF: 0.782 AC: 2708 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.88

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: rs4899056; hg19: chr14-62189531;