Variant chr14-61727521-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_001530.4(HIF1A):c.639G>A(p.Lys213=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,613,694 control chromosomes in the GnomAD database, including 507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.029 ( 97 hom., cov: 32)

Exomes 𝑓: 0.021 ( 410 hom. )

Consequence

HIF1A
NM_001530.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.35

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:54284): (HIF1A antisense RNA 3)

HIF1A-AS3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-61727521-G-A is Benign according to our data. Variant chr14-61727521-G-A is described in ClinVar as [Benign]. Clinvar id is 2920757.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.35 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.057 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
HIF1A	NM_001530.4 linkuse as main transcript	c.639G>A	p.Lys213=	synonymous_variant	6/15	ENST00000337138.9
HIF1A-AS3	NR_144368.1 linkuse as main transcript	n.214-10504C>T		intron_variant, non_coding_transcript_variant
HIF1A	NM_001243084.2 linkuse as main transcript	c.711G>A	p.Lys237=	synonymous_variant	6/15
HIF1A	NM_181054.3 linkuse as main transcript	c.639G>A	p.Lys213=	synonymous_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HIF1A	ENST00000337138.9 linkuse as main transcript	c.639G>A	p.Lys213=	synonymous_variant	6/15	1	NM_001530.4	P4	Q16665-1
HIF1A-AS3	ENST00000660325.2 linkuse as main transcript	n.216-13519C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0286

AC:

4346

AN:

151954

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0587

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0141

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0178

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0207

Gnomad OTH

AF:

0.0234

GnomAD3 exomes

AF:

0.0176

AC:

4414

AN:

251410

Hom.:

AF XY:

0.0167

AC XY:

2270

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0603

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.00913

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00493

Gnomad FIN exome

AF:

0.0191

Gnomad NFE exome

AF:

0.0202

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0206

AC:

30135

AN:

1461622

Hom.:

410

Cov.:

AF XY:

0.0200

AC XY:

14514

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.0603

Gnomad4 AMR exome

AF:

0.0107

Gnomad4 ASJ exome

AF:

0.00815

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00565

Gnomad4 FIN exome

AF:

0.0179

Gnomad4 NFE exome

AF:

0.0222

Gnomad4 OTH exome

AF:

0.0206

GnomAD4 genome

AF:

0.0287

AC:

4361

AN:

152072

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

2060

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.0589

Gnomad4 AMR

AF:

0.0140

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00498

Gnomad4 FIN

AF:

0.0178

Gnomad4 NFE

AF:

0.0207

Gnomad4 OTH

AF:

0.0232

Alfa

AF:

0.0242

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.0189

EpiControl

AF:

0.0176

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 30, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over