rs4902080

Variant names:

• chr14-61741287-T-C
• rs4902080
• NM_001530.4:c.2093+99T>C

Your query was ambiguous. Multiple possible variants found:

• chr14-61741287-T-C
• chr14-61741287-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001530.4(HIF1A):​c.2093+99T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 804,300 control chromosomes in the GnomAD database, including 348,015 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 0.87 (58482 hom., cov: 31)
  • Exomes 𝑓: 0.94 (289533 hom.)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 10 publications found

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-AS3 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.2093+99T>C		intron_variant	Intron 12 of 14	ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.2165+99T>C		intron_variant	Intron 12 of 14		NP_001230013.1
HIF1A	NM_181054.3	c.2093+99T>C		intron_variant	Intron 12 of 13		NP_851397.1
HIF1A-AS3	NR_144368.1	n.213+9598A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.2093+99T>C		intron_variant	Intron 12 of 14	1	NM_001530.4	ENSP00000338018.4

Frequencies

GnomAD3 genomes AF: 0.868 AC: 131751 AN: 151860 Hom.: 58473 Cov.: 31

Gnomad AFR AF: 0.659

Gnomad AMI AF: 0.978

Gnomad AMR AF: 0.928

Gnomad ASJ AF: 0.901

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.975

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.882

GnomAD4 exome AF: 0.940 AC: 613247 AN: 652326 Hom.: 289533 AF XY: 0.938 AC XY: 315373 AN XY: 336276

African (AFR) AF: 0.661 AC: 10342 AN: 15656

American (AMR) AF: 0.949 AC: 18233 AN: 19216

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 13736 AN: 14974

East Asian (EAS) AF: 0.856 AC: 27414 AN: 32028

South Asian (SAS) AF: 0.852 AC: 38999 AN: 45800

European-Finnish (FIN) AF: 0.973 AC: 42440 AN: 43612

Middle Eastern (MID) AF: 0.886 AC: 3319 AN: 3744

European-Non Finnish (NFE) AF: 0.964 AC: 428896 AN: 444940

Other (OTH) AF: 0.923 AC: 29868 AN: 32356

GnomAD4 genome AF: 0.867 AC: 131808 AN: 151974 Hom.: 58482 Cov.: 31 AF XY: 0.867 AC XY: 64409 AN XY: 74276

African (AFR) AF: 0.659 AC: 27250 AN: 41374

American (AMR) AF: 0.928 AC: 14179 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.901 AC: 3128 AN: 3470

East Asian (EAS) AF: 0.849 AC: 4391 AN: 5174

South Asian (SAS) AF: 0.846 AC: 4079 AN: 4822

European-Finnish (FIN) AF: 0.975 AC: 10249 AN: 10514

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65514 AN: 68024

Other (OTH) AF: 0.883 AC: 1864 AN: 2110

Alfa AF: 0.932 Hom.: 79371

Bravo AF: 0.857

Asia WGS AF: 0.850 AC: 2953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.38
DANN	Benign	0.67
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4902080; hg19: chr14-62208005;