rs3826795

Variant names:

• chr19-46297176-G-A
• rs3826795
• NM_152795.4:c.26+74G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-46297176-G-A
• chr19-46297176-G-C
• chr19-46297176-G-T

Variant summary

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

The NM_152795.4(HIF3A):​c.26+74G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 634,342 control chromosomes in the GnomAD database, including 13,522 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 0.21 (3256 hom., cov: 27)
  • Exomes 𝑓: 0.15 (10266 hom.)
• Consequence: HIF3A NM_152795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

Genes affected

HIF3A (HGNC:15825): (hypoxia inducible factor 3 subunit alpha) The protein encoded by this gene is the alpha-3 subunit of one of several alpha/beta-subunit heterodimeric transcription factors that regulate many adaptive responses to low oxygen tension (hypoxia). The alpha-3 subunit lacks the transactivation domain found in factors containing either the alpha-1 or alpha-2 subunits. It is thought that factors containing the alpha-3 subunit are negative regulators of hypoxia-inducible gene expression. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF3A	NM_152795.4	c.26+74G>A		intron_variant	Intron 1 of 14	ENST00000377670.9	NP_690008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF3A	ENST00000377670.9	c.26+74G>A		intron_variant	Intron 1 of 14	1	NM_152795.4	ENSP00000366898.3
HIF3A	ENST00000244302.8	n.57+74G>A		intron_variant	Intron 1 of 12	1
HIF3A	ENST00000475432.6	n.57+74G>A		intron_variant	Intron 1 of 6	1
HIF3A	ENST00000533789.5	n.26+74G>A		intron_variant	Intron 1 of 4	4		ENSP00000432809.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 30201 AN: 147348 Hom.: 3243 Cov.: 27

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.485

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.260

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.146 AC: 71296 AN: 486876 Hom.: 10266 AF XY: 0.153 AC XY: 37374 AN XY: 243672

Gnomad4 AFR exome AF: 0.0891

Gnomad4 AMR exome AF: 0.327

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.249

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.205 AC: 30239 AN: 147466 Hom.: 3256 Cov.: 27 AF XY: 0.208 AC XY: 14935 AN XY: 71818

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.303

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.246

Alfa AF: 0.218 Hom.: 7580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.7
DANN	Benign	0.61

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: rs3826795; hg19: chr19-46800433; COSMIC: COSV52196784; COSMIC: COSV52196784;