rs7143164

Variant names:

• chr14-61700037-G-C
• rs7143164
• NM_001530.4:c.35+4198G>C

Variant summary

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

The NM_001530.4(HIF1A):​c.35+4198G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,940 control chromosomes in the GnomAD database, including 6,553 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 (6553 hom., cov: 32)
• Consequence: HIF1A NM_001530.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520
• Publications: 14 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HIF1A	NM_001530.4	c.35+4198G>C		intron_variant	Intron 1 of 14	ENST00000337138.9	NP_001521.1
HIF1A	NM_001243084.2	c.104+2083G>C		intron_variant	Intron 1 of 14		NP_001230013.1
HIF1A	NM_181054.3	c.35+4198G>C		intron_variant	Intron 1 of 13		NP_851397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HIF1A	ENST00000337138.9	c.35+4198G>C		intron_variant	Intron 1 of 14	1	NM_001530.4	ENSP00000338018.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33927 AN: 151822 Hom.: 6548 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.0614

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.0930

Gnomad OTH AF: 0.214

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 33963 AN: 151940 Hom.: 6553 Cov.: 32 AF XY: 0.219 AC XY: 16262 AN XY: 74288

African (AFR) AF: 0.526 AC: 21734 AN: 41352

American (AMR) AF: 0.148 AC: 2262 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 682 AN: 3466

East Asian (EAS) AF: 0.165 AC: 857 AN: 5180

South Asian (SAS) AF: 0.221 AC: 1066 AN: 4822

European-Finnish (FIN) AF: 0.0446 AC: 471 AN: 10568

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6316 AN: 67950

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.167 Hom.: 493

Bravo AF: 0.241

Asia WGS AF: 0.191 AC: 662 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.62
PhyloP100		0.52
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: rs7143164; hg19: chr14-62166755;