19-46331426-A-G

Variant names:

• chr19-46331426-A-G
• rs11665853
• ENST00000244302.8:n.2014A>G

Variant summary

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

The ENST00000244302.8(HIF3A):​n.2014A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 434,890 control chromosomes in the GnomAD database, including 7,467 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 0.12 (1402 hom., cov: 28)
  • Exomes 𝑓: 0.20 (6065 hom.)
• Consequence: HIF3A ENST00000244302.8 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.560
• Publications: 6 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]

ENSG00000269124 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF3A	NM_152795.4	c.1830+153A>G		intron_variant	Intron 13 of 14	ENST00000377670.9	NP_690008.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF3A	ENST00000377670.9	c.1830+153A>G		intron_variant	Intron 13 of 14	1	NM_152795.4	ENSP00000366898.3

Frequencies

GnomAD3 genomes AF: 0.120 AC: 16615 AN: 139006 Hom.: 1392 Cov.: 28

Gnomad AFR AF: 0.0292

Gnomad AMI AF: 0.0276

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0938

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.199 AC: 58893 AN: 295802 Hom.: 6065 Cov.: 5 AF XY: 0.197 AC XY: 31134 AN XY: 157730

African (AFR) AF: 0.0467 AC: 340 AN: 7288

American (AMR) AF: 0.349 AC: 6212 AN: 17786

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 2102 AN: 7930

East Asian (EAS) AF: 0.488 AC: 11022 AN: 22590

South Asian (SAS) AF: 0.162 AC: 6591 AN: 40798

European-Finnish (FIN) AF: 0.114 AC: 3309 AN: 29058

Middle Eastern (MID) AF: 0.213 AC: 314 AN: 1474

European-Non Finnish (NFE) AF: 0.168 AC: 25892 AN: 154236

Other (OTH) AF: 0.212 AC: 3111 AN: 14642

GnomAD4 genome AF: 0.120 AC: 16641 AN: 139088 Hom.: 1402 Cov.: 28 AF XY: 0.125 AC XY: 8322 AN XY: 66824

African (AFR) AF: 0.0292 AC: 1081 AN: 37046

American (AMR) AF: 0.274 AC: 3635 AN: 13288

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 608 AN: 3382

East Asian (EAS) AF: 0.381 AC: 1739 AN: 4568

South Asian (SAS) AF: 0.199 AC: 830 AN: 4172

European-Finnish (FIN) AF: 0.0938 AC: 768 AN: 8184

Middle Eastern (MID) AF: 0.198 AC: 52 AN: 262

European-Non Finnish (NFE) AF: 0.117 AC: 7616 AN: 65346

Other (OTH) AF: 0.146 AC: 288 AN: 1970

Alfa AF: 0.118 Hom.: 2673

Bravo AF: 0.121

Asia WGS AF: 0.247 AC: 856 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.73
PhyloP100		-0.56
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: rs11665853; hg19: chr19-46834683;