rs1060619

Positions:

• chr12-6535615-T-C

Variant summary

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

The NM_002046.7(GAPDH):​c.29+754T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 246,346 control chromosomes in the GnomAD database, including 10,945 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 0.31 (8385 hom., cov: 32)
  • Exomes 𝑓: 0.23 (2560 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.180

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GAPDH	NM_002046.7	c.29+754T>C		intron_variant		ENST00000229239.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GAPDH	ENST00000229239.10	c.29+754T>C		intron_variant		1	NM_002046.7	P1

Frequencies

GnomAD3 genomes AF: 0.306 AC: 46401 AN: 151834 Hom.: 8357 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.260

GnomAD4 exome AF: 0.227 AC: 21448 AN: 94394 Hom.: 2560 AF XY: 0.226 AC XY: 10264 AN XY: 45336

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.433

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.506

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.219

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.306 AC: 46477 AN: 151952 Hom.: 8385 Cov.: 32 AF XY: 0.308 AC XY: 22840 AN XY: 74262

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.282

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.489

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.264

Alfa AF: 0.229 Hom.: 2667

Bravo AF: 0.316

Asia WGS AF: 0.425 AC: 1476 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.7
DANN	Benign	0.72

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: rs1060619; hg19: chr12-6644781;