14-61704708-A-C

Variant names:

• chr14-61704708-A-C
• rs1951795
• NM_001530.4:c.35+8869A>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.35+8869A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 152,090 control chromosomes in the GnomAD database, including 36,902 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 0.65 (36902 hom., cov: 33)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679
• Publications: 27 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:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 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.35+8869A>C		intron	N/A	NP_001521.1
	HIF1A	NM_001243084.2		c.104+6754A>C		intron	N/A	NP_001230013.1
	HIF1A	NM_181054.3		c.35+8869A>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.35+8869A>C		intron	N/A	ENSP00000338018.4
	HIF1A	ENST00000539097.2	TSL:1	c.104+6754A>C		intron	N/A	ENSP00000437955.1
	HIF1A	ENST00000394997.5	TSL:1	c.35+8869A>C		intron	N/A	ENSP00000378446.1

Frequencies

GnomAD3 genomes AF: 0.646 AC: 98142 AN: 151972 Hom.: 36891 Cov.: 33

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.918

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.646 AC: 98185 AN: 152090 Hom.: 36902 Cov.: 33 AF XY: 0.653 AC XY: 48579 AN XY: 74356

African (AFR) AF: 0.233 AC: 9684 AN: 41490

American (AMR) AF: 0.755 AC: 11531 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2341 AN: 3472

East Asian (EAS) AF: 0.780 AC: 4040 AN: 5178

South Asian (SAS) AF: 0.676 AC: 3260 AN: 4824

European-Finnish (FIN) AF: 0.918 AC: 9737 AN: 10602

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55280 AN: 67932

Other (OTH) AF: 0.653 AC: 1375 AN: 2106

Alfa AF: 0.744 Hom.: 78291

Bravo AF: 0.617

Asia WGS AF: 0.713 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	6.5
DANN	Benign	0.88
PhyloP100		-0.68
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: rs1951795; hg19: chr14-62171426;