rs2301113

Positions:

• chr14-61739830-C-A
• chr14-61739830-C-G
• chr14-61739830-C-T

Variant summary

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

The NM_001530.4(HIF1A):​c.1537-675C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,960 control chromosomes in the GnomAD database, including 32,747 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 0.60 (32747 hom., cov: 31)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.57

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:54284): (HIF1A antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIF1A	NM_001530.4	c.1537-675C>A		intron_variant		ENST00000337138.9
HIF1A-AS3	NR_144368.1	n.213+11055G>T		intron_variant, non_coding_transcript_variant
HIF1A	NM_001243084.2	c.1609-675C>A		intron_variant
HIF1A	NM_181054.3	c.1537-675C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9	c.1537-675C>A		intron_variant		1	NM_001530.4	P4
HIF1A-AS3	ENST00000660325.2	n.215+11055G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91467 AN: 151842 Hom.: 32741 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.828

Gnomad AMR AF: 0.702

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.628

Gnomad FIN AF: 0.885

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.774

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.602 AC: 91482 AN: 151960 Hom.: 32747 Cov.: 31 AF XY: 0.609 AC XY: 45222 AN XY: 74266

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.885

Gnomad4 NFE AF: 0.774

Gnomad4 OTH AF: 0.606

Alfa AF: 0.697 Hom.: 10882

Bravo AF: 0.572

Asia WGS AF: 0.640 AC: 2225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.076
DANN	Benign	0.49

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: rs2301113; hg19: chr14-62206548;