Genetic Variant NM_017902.3:c.*5713A>G (chr10-100553850-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.567

Publications

14 publications found

Variant links:

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]

HIF1AN links:

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ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017902.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HIF1AN	NM_017902.3	MANE Select	c.*5713A>G		3_prime_UTR	Exon 8 of 8	NP_060372.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
HIF1AN	ENST00000299163.7	TSL:1 MANE Select	c.*5713A>G	3_prime_UTR	Exon 8 of 8	ENSP00000299163.4
HIF1AN	ENST00000860850.1		c.*5713A>G	3_prime_UTR	Exon 8 of 8	ENSP00000530909.1
HIF1AN	ENST00000935501.1		c.*5713A>G	3_prime_UTR	Exon 8 of 8	ENSP00000605560.1

Frequencies

GnomAD3 genomes

AF:

0.220

AC:

33461

AN:

152012

Hom.:

3808

Cov.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.220

AC:

33484

AN:

152130

Hom.:

3816

Cov.:

AF XY:

0.219

AC XY:

16273

AN XY:

74352

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.216

AC:

14714

AN:

67996

Other (OTH)

AF:

0.218

AC:

459

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1344

2687

4031

5374

6718

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over