rs11292

Positions:

• chr10-100553850-A-G

Variant summary

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

The NM_017902.3(HIF1AN):​c.*5713A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,138 control chromosomes in the GnomAD database, including 3,816 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 0.22 (3816 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: HIF1AN NM_017902.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.567

Genes affected

HIF1AN (HGNC:17113): (hypoxia inducible factor 1 subunit alpha inhibitor) Enables several functions, including 2-oxoglutarate-dependent dioxygenase activity; NF-kappaB binding activity; and transition metal ion binding activity. Involved in several processes, including negative regulation of Notch signaling pathway; negative regulation of transcription from RNA polymerase II promoter in response to hypoxia; and protein hydroxylation. Located in cytosol; nucleoplasm; and perinuclear region of cytoplasm. Colocalizes with nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HIF1AN	NM_017902.3	c.*5713A>G		3_prime_UTR_variant	8/8	ENST00000299163.7
HIF1AN	XM_011539940.3	c.*5713A>G		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1AN	ENST00000299163.7	c.*5713A>G		3_prime_UTR_variant	8/8	1	NM_017902.3	P1

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33461 AN: 152012 Hom.: 3808 Cov.: 32

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.220

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.220 AC: 33484 AN: 152130 Hom.: 3816 Cov.: 32 AF XY: 0.219 AC XY: 16273 AN XY: 74352

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.218

Alfa AF: 0.216 Hom.: 1310

Bravo AF: 0.220

Asia WGS AF: 0.181 AC: 628 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.86

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: rs11292; hg19: chr10-102313607;