rs1060621

Positions:

• chr12-6535530-T-G

Variant summary

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

The NM_002046.7(GAPDH):​c.29+669T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 842,918 control chromosomes in the GnomAD database, including 16,801 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 0.19 (3039 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13762 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPDH	NM_002046.7	c.29+669T>G		intron_variant		ENST00000229239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPDH	ENST00000229239.10	c.29+669T>G		intron_variant		1	NM_002046.7	P1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29563 AN: 152020 Hom.: 3035 Cov.: 33

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.197 AC: 136399 AN: 690780 Hom.: 13762 AF XY: 0.197 AC XY: 63168 AN XY: 321422

Gnomad4 AFR exome AF: 0.167

Gnomad4 AMR exome AF: 0.210

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.155

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.194 AC: 29576 AN: 152138 Hom.: 3039 Cov.: 33 AF XY: 0.194 AC XY: 14405 AN XY: 74400

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.367

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.173

Alfa AF: 0.192 Hom.: 598

Bravo AF: 0.196

Asia WGS AF: 0.240 AC: 833 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.72

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

Other links and lift over

dbSNP: rs1060621; hg19: chr12-6644696;