rs11190604

Positions:

• chr10-100542700-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.577+1918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,068 control chromosomes in the GnomAD database, including 2,922 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 0.19 (2922 hom., cov: 31)
• Consequence: HIF1AN NM_017902.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HIF1AN	NM_017902.3	c.577+1918A>G		intron_variant		ENST00000299163.7	NP_060372.2
HIF1AN	XM_011539940.3	c.637+1918A>G		intron_variant			XP_011538242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HIF1AN	ENST00000299163.7	c.577+1918A>G		intron_variant		1	NM_017902.3	ENSP00000299163	P1
HIF1AN	ENST00000533589.6	c.256+1918A>G		intron_variant		3		ENSP00000433360
HIF1AN	ENST00000526476.5	c.*384+1918A>G		intron_variant, NMD_transcript_variant		3		ENSP00000432791
HIF1AN	ENST00000478787.1	n.341+1918A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29057 AN: 151950 Hom.: 2919 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.191 AC: 29059 AN: 152068 Hom.: 2922 Cov.: 31 AF XY: 0.191 AC XY: 14228 AN XY: 74322

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.216

Gnomad4 OTH AF: 0.190

Alfa AF: 0.203 Hom.: 1017

Bravo AF: 0.186

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.42

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: rs11190604; hg19: chr10-102302457;