Genetic Variant NM_002046.7:c.29+695A>G (chr12-6535556-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002046.7(GAPDH):c.29+695A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 610,906 control chromosomes in the GnomAD database, including 21,377 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 0.32 ( 9272 hom., cov: 32)

Exomes 𝑓: 0.23 ( 12105 hom. )

Consequence

GAPDH
NM_002046.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.149

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDH	NM_002046.7 link	c.29+695A>G		intron_variant	Intron 2 of 8	ENST00000229239.10	NP_002037.2	P04406-1V9HVZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239.10 link	c.29+695A>G		intron_variant	Intron 2 of 8	1	NM_002046.7	ENSP00000229239.5		P04406-1

Frequencies

GnomAD3 genomes

AF:

0.320

AC:

48546

AN:

151894

Hom.:

9242

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.297

Gnomad ASJ

AF:

0.175

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.277

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.273

GnomAD4 exome

AF:

0.226

AC:

103657

AN:

458894

Hom.:

12105

AF XY:

0.224

AC XY:

48141

AN XY:

214908

show subpopulations

Gnomad4 AFR exome

AF:

0.531

Gnomad4 AMR exome

AF:

0.280

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.507

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.320

AC:

48624

AN:

152012

Hom.:

9272

Cov.:

AF XY:

0.322

AC XY:

23901

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.522

Gnomad4 AMR

AF:

0.297

Gnomad4 ASJ

AF:

0.175

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.263

Gnomad4 FIN

AF:

0.277

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.245

Hom.:

1607

Bravo

AF:

0.331

Asia WGS

AF:

0.429

AC:

1489

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

9.9

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over