dbSNP rs10873142: HIF1A:c.1029-145C>T (chr14-61736744-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001530.4(HIF1A):c.1029-145C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.752 in 618,868 control chromosomes in the GnomAD database, including 181,797 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 0.67 ( 38057 hom., cov: 32)

Exomes 𝑓: 0.78 ( 143740 hom. )

Consequence

HIF1A
NM_001530.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.320

Publications

29 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:

HIF1A-AS3 (HGNC:):

HIF1A-AS3 links:

HIF1A-AS3 (HGNC:54284): (HIF1A antisense RNA 3)

HIF1A-AS3 links:

Genome browser will be placed here

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=-0.95).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
HIF1A	NM_001530.4 link	c.1029-145C>T	intron_variant	Intron 8 of 14	ENST00000337138.9	NP_001521.1	Q16665-1D0VY79
HIF1A	NM_001243084.2 link	c.1101-145C>T	intron_variant	Intron 8 of 14		NP_001230013.1	Q16665-3
HIF1A	NM_181054.3 link	c.1029-145C>T	intron_variant	Intron 8 of 13		NP_851397.1	Q16665-2
HIF1A-AS3	NR_144368.1 link	n.213+14141G>A	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9 link	c.1029-145C>T		intron_variant	Intron 8 of 14	1	NM_001530.4	ENSP00000338018.4		Q16665-1

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102428

AN:

152002

Hom.:

38034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.835

Gnomad AMR

AF:

0.749

Gnomad ASJ

AF:

0.668

Gnomad EAS

AF:

0.764

Gnomad SAS

AF:

0.676

Gnomad FIN

AF:

0.919

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.673

GnomAD4 exome

AF:

0.778

AC:

363143

AN:

466748

Hom.:

143740

AF XY:

0.775

AC XY:

191282

AN XY:

246890

show subpopulations

African (AFR)

AF:

0.345

AC:

4396

AN:

12756

American (AMR)

AF:

0.781

AC:

15301

AN:

19598

Ashkenazi Jewish (ASJ)

AF:

0.674

AC:

9495

AN:

14092

East Asian (EAS)

AF:

0.766

AC:

24067

AN:

31408

South Asian (SAS)

AF:

0.683

AC:

31309

AN:

45834

European-Finnish (FIN)

AF:

0.909

AC:

31954

AN:

35150

Middle Eastern (MID)

AF:

0.645

AC:

1301

AN:

2016

European-Non Finnish (NFE)

AF:

0.807

AC:

225437

AN:

279234

Other (OTH)

AF:

0.746

AC:

19883

AN:

26660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3871

7742

11612

15483

19354

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

932

1864

2796

3728

4660

<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:

0.674

AC:

102501

AN:

152120

Hom.:

38057

Cov.:

AF XY:

0.681

AC XY:

50680

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.340

AC:

14098

AN:

41440

American (AMR)

AF:

0.749

AC:

11459

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.668

AC:

2319

AN:

3472

East Asian (EAS)

AF:

0.765

AC:

3958

AN:

5174

South Asian (SAS)

AF:

0.675

AC:

3255

AN:

4824

European-Finnish (FIN)

AF:

0.919

AC:

9741

AN:

10602

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.813

AC:

55303

AN:

67996

Other (OTH)

AF:

0.676

AC:

1430

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1357

2714

4070

5427

6784

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.719

Hom.:

6142

Bravo

AF:

0.649

Asia WGS

AF:

0.714

AC:

2483

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

3.5

(source)

DANN

Benign

0.38

PhyloP100

0.32

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over