rs3741918

Positions:

• chr12-6535090-T-A

Variant summary

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

The NM_002046.7(GAPDH):​c.29+229T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 759,242 control chromosomes in the GnomAD database, including 16,848 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 (3655 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13193 hom.)
• Consequence: GAPDH NM_002046.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GAPDH	NM_002046.7	c.29+229T>A		intron_variant		ENST00000229239.10	NP_002037.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239.10	c.29+229T>A		intron_variant		1	NM_002046.7	ENSP00000229239.5

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32704 AN: 152024 Hom.: 3649 Cov.: 33

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.0877

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.192

GnomAD4 exome AF: 0.201 AC: 122172 AN: 607098 Hom.: 13193 Cov.: 8 AF XY: 0.197 AC XY: 60628 AN XY: 308154

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.217

Gnomad4 ASJ exome AF: 0.0922

Gnomad4 EAS exome AF: 0.312

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.230

Gnomad4 NFE exome AF: 0.204

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.215 AC: 32725 AN: 152144 Hom.: 3655 Cov.: 33 AF XY: 0.213 AC XY: 15868 AN XY: 74390

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.217

Gnomad4 ASJ AF: 0.0877

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.189

Alfa AF: 0.213 Hom.: 449

Bravo AF: 0.218

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	3.0
DANN	Benign	0.58

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: rs3741918; hg19: chr12-6644256;