Genetic Variant HIF1A:c.-9delT (chr14-61697832-AT-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001243084.2(HIF1A):c.-9delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00448 in 1,402,824 control chromosomes in the GnomAD database, including 174 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 97 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 77 hom. )

Consequence

HIF1A
NM_001243084.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.274

Publications

0 publications found

Variant links:

Genes affected

HIF1A (HGNC:4910): (hypoxia inducible factor 1 subunit alpha) This gene encodes the alpha subunit of transcription factor hypoxia-inducible factor-1 (HIF-1), which is a heterodimer composed of an alpha and a beta subunit. HIF-1 functions as a master regulator of cellular and systemic homeostatic response to hypoxia by activating transcription of many genes, including those involved in energy metabolism, angiogenesis, apoptosis, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. HIF-1 thus plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2011]

HIF1A links:

ENSG00000258667 (HGNC:):

ENSG00000258667 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 14-61697832-AT-A is Benign according to our data. Variant chr14-61697832-AT-A is described in ClinVar as Benign. ClinVar VariationId is 2920767.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243084.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HIF1A	NM_001530.4	MANE Select	c.35+2003delT	intron	N/A	NP_001521.1	D0VY79
HIF1A	NM_001243084.2		c.-9delT	5_prime_UTR	Exon 1 of 15	NP_001230013.1	Q16665-3
HIF1A	NM_181054.3		c.35+2003delT	intron	N/A	NP_851397.1	Q16665-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HIF1A	ENST00000539097.2	TSL:1	c.-9delT	5_prime_UTR	Exon 1 of 15	ENSP00000437955.1	Q16665-3
HIF1A	ENST00000337138.9	TSL:1 MANE Select	c.35+2003delT	intron	N/A	ENSP00000338018.4	Q16665-1
HIF1A	ENST00000394997.5	TSL:1	c.35+2003delT	intron	N/A	ENSP00000378446.1	A8MYV6

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2804

AN:

150592

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00810

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00579

Gnomad SAS

AF:

0.000629

Gnomad FIN

AF:

0.00117

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000296

Gnomad OTH

AF:

0.0189

GnomAD2 exomes

AF:

0.0156

AC:

706

AN:

45182

AF XY:

0.0131

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.0164

Gnomad ASJ exome

AF:

0.00524

Gnomad EAS exome

AF:

0.0201

Gnomad FIN exome

AF:

0.00562

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00276

AC:

3451

AN:

1252116

Hom.:

Cov.:

AF XY:

0.00260

AC XY:

1600

AN XY:

615848

show subpopulations

African (AFR)

AF:

0.0711

AC:

1929

AN:

27126

American (AMR)

AF:

0.00788

AC:

177

AN:

22466

Ashkenazi Jewish (ASJ)

AF:

0.00124

AC:

AN:

21024

East Asian (EAS)

AF:

0.00552

AC:

175

AN:

31722

South Asian (SAS)

AF:

0.00208

AC:

135

AN:

64880

European-Finnish (FIN)

AF:

0.00167

AC:

AN:

29372

Middle Eastern (MID)

AF:

0.00410

AC:

AN:

5126

European-Non Finnish (NFE)

AF:

0.000565

AC:

564

AN:

998504

Other (OTH)

AF:

0.00723

AC:

375

AN:

51896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

118

235

353

470

588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0188

AC:

2832

AN:

150708

Hom.:

Cov.:

AF XY:

0.0187

AC XY:

1380

AN XY:

73624

show subpopulations

African (AFR)

AF:

0.0632

AC:

2604

AN:

41180

American (AMR)

AF:

0.00809

AC:

122

AN:

15088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3448

East Asian (EAS)

AF:

0.00580

AC:

AN:

5170

South Asian (SAS)

AF:

0.000630

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00117

AC:

AN:

10300

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000296

AC:

AN:

67474

Other (OTH)

AF:

0.0187

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

126

252

377

503

629

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.00558

Hom.:

Bravo

AF:

0.0215

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.27

Mutation Taster

=299/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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