rs12461322

Variant names:

• chr19-46312053-G-A
• rs12461322
• NM_152795.4:c.771-108G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-46312053-G-A
• chr19-46312053-G-C
• chr19-46312053-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152795.4(HIF3A):​c.771-108G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 840,490 control chromosomes in the GnomAD database, including 9,085 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 0.10 (1213 hom., cov: 31)
  • Exomes 𝑓: 0.13 (7872 hom.)
• Consequence: HIF3A NM_152795.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469
• Publications: 8 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF3A	NM_152795.4	c.771-108G>A		intron_variant	Intron 6 of 14	ENST00000377670.9	NP_690008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF3A	ENST00000377670.9	c.771-108G>A		intron_variant	Intron 6 of 14	1	NM_152795.4	ENSP00000366898.3

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15348 AN: 151704 Hom.: 1212 Cov.: 31

Gnomad AFR AF: 0.0236

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0696

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.142 AC: 35333 AN: 248270 AF XY: 0.138

Gnomad AFR exome AF: 0.0231

Gnomad AMR exome AF: 0.275

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.310

Gnomad FIN exome AF: 0.0740

Gnomad NFE exome AF: 0.0983

Gnomad OTH exome AF: 0.137

GnomAD4 exome AF: 0.130 AC: 89825 AN: 688668 Hom.: 7872 Cov.: 9 AF XY: 0.130 AC XY: 48159 AN XY: 371542

African (AFR) AF: 0.0229 AC: 430 AN: 18782

American (AMR) AF: 0.270 AC: 11811 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 3940 AN: 21394

East Asian (EAS) AF: 0.352 AC: 12768 AN: 36316

South Asian (SAS) AF: 0.152 AC: 10749 AN: 70696

European-Finnish (FIN) AF: 0.0715 AC: 3587 AN: 50178

Middle Eastern (MID) AF: 0.125 AC: 535 AN: 4278

European-Non Finnish (NFE) AF: 0.102 AC: 41468 AN: 408192

Other (OTH) AF: 0.129 AC: 4537 AN: 35054

GnomAD4 genome AF: 0.101 AC: 15358 AN: 151822 Hom.: 1213 Cov.: 31 AF XY: 0.105 AC XY: 7799 AN XY: 74208

African (AFR) AF: 0.0236 AC: 975 AN: 41388

American (AMR) AF: 0.226 AC: 3443 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1650 AN: 5146

South Asian (SAS) AF: 0.162 AC: 780 AN: 4808

European-Finnish (FIN) AF: 0.0696 AC: 734 AN: 10544

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6801 AN: 67936

Other (OTH) AF: 0.133 AC: 279 AN: 2100

Alfa AF: 0.108 Hom.: 3375

Bravo AF: 0.111

Asia WGS AF: 0.221 AC: 770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.55
PhyloP100		-0.47
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: rs12461322; hg19: chr19-46815310; COSMIC: COSV52199745; COSMIC: COSV52199745;