rs7307229

Variant names:

• chr12-6534437-C-G
• rs7307229
• NM_002046.7:c.-156C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002046.7(GAPDH):​c.-156C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 320,268 control chromosomes in the GnomAD database, including 1,079 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 0.067 (1009 hom., cov: 33)
  • Exomes 𝑓: 0.012 (70 hom.)
• Consequence: GAPDH NM_002046.7 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09

Genes affected

GAPDH (HGNC:4141): (glyceraldehyde-3-phosphate dehydrogenase) This gene encodes a member of the glyceraldehyde-3-phosphate dehydrogenase protein family. The encoded protein has been identified as a moonlighting protein based on its ability to perform mechanistically distinct functions. The product of this gene catalyzes an important energy-yielding step in carbohydrate metabolism, the reversible oxidative phosphorylation of glyceraldehyde-3-phosphate in the presence of inorganic phosphate and nicotinamide adenine dinucleotide (NAD). The encoded protein has additionally been identified to have uracil DNA glycosylase activity in the nucleus. Also, this protein contains a peptide that has antimicrobial activity against E. coli, P. aeruginosa, and C. albicans. Studies of a similar protein in mouse have assigned a variety of additional functions including nitrosylation of nuclear proteins, the regulation of mRNA stability, and acting as a transferrin receptor on the cell surface of macrophage. Many pseudogenes similar to this locus are present in the human genome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

GAPDH-DT (HGNC:55492): (GAPDH divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDH	NM_002046.7	c.-156C>G		upstream_gene_variant		ENST00000229239.10	NP_002037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239.10	c.-156C>G		upstream_gene_variant		1	NM_002046.7	ENSP00000229239.5

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10099 AN: 151936 Hom.: 999 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000974

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.0124 AC: 2085 AN: 168206 Hom.: 70 Cov.: 0 AF XY: 0.0162 AC XY: 1515 AN XY: 93740

Gnomad4 AFR exome AF: 0.144

Gnomad4 AMR exome AF: 0.0124

Gnomad4 ASJ exome AF: 0.00884

Gnomad4 EAS exome AF: 0.000260

Gnomad4 SAS exome AF: 0.0400

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00205

Gnomad4 OTH exome AF: 0.0140

GnomAD4 genome AF: 0.0667 AC: 10146 AN: 152062 Hom.: 1009 Cov.: 33 AF XY: 0.0655 AC XY: 4869 AN XY: 74354

Gnomad4 AFR AF: 0.220

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.0121

Gnomad4 EAS AF: 0.000976

Gnomad4 SAS AF: 0.0451

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00284

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0514 Hom.: 70

Bravo AF: 0.0748

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.36
DANN	Benign	0.69

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

LitVar

Other links and lift over

dbSNP: rs7307229; hg19: chr12-6643603;