10-100553850-A-G

Variant names:

• chr10-100553850-A-G
• rs11292
• NM_017902.3:c.*5713A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
HIF1AN	NM_017902.3	c.*5713A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000299163.7	NP_060372.2
HIF1AN	XM_011539940.3	c.*5713A>G		3_prime_UTR_variant	Exon 8 of 8		XP_011538242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1AN	ENST00000299163.7	c.*5713A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_017902.3	ENSP00000299163.4

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 2 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.263 AC: 10895 AN: 41470

American (AMR) AF: 0.177 AC: 2706 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 674 AN: 3472

East Asian (EAS) AF: 0.107 AC: 553 AN: 5176

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4820

European-Finnish (FIN) AF: 0.204 AC: 2158 AN: 10586

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14714 AN: 67996

Other (OTH) AF: 0.218 AC: 459 AN: 2110

Alfa AF: 0.217 Hom.: 1609

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
PhyloP100		0.57
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: rs11292; hg19: chr10-102313607;