12-6534825-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002046.7(GAPDH):c.-8C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,612,562 control chromosomes in the GnomAD database, including 55,507 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5213 hom., cov: 33)

Exomes 𝑓: 0.26 ( 50294 hom. )

Consequence

GAPDH
NM_002046.7 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.214

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 12-6534825-C-G is Benign according to our data. Variant chr12-6534825-C-G is described in ClinVar as [Benign]. Clinvar id is 1262368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GAPDH	NM_002046.7 link	c.-8C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	ENST00000229239.10	NP_002037.2	P04406-1V9HVZ4
GAPDH	NM_002046.7 link	c.-8C>G		5_prime_UTR_variant	Exon 2 of 9	ENST00000229239.10	NP_002037.2	P04406-1V9HVZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GAPDH	ENST00000229239 link	c.-8C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 9	1	NM_002046.7	ENSP00000229239.5		P04406-1
GAPDH	ENST00000229239 link	c.-8C>G		5_prime_UTR_variant	Exon 2 of 9	1	NM_002046.7	ENSP00000229239.5		P04406-1

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39529

AN:

152054

Hom.:

5201

Cov.:

show subpopulations

Gnomad AFR

AF:

0.287

Gnomad AMI

AF:

0.203

Gnomad AMR

AF:

0.241

Gnomad ASJ

AF:

0.111

Gnomad EAS

AF:

0.219

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.258

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.237

AC:

59104

AN:

248998

Hom.:

7396

AF XY:

0.232

AC XY:

31306

AN XY:

135000

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.114

Gnomad EAS exome

AF:

0.219

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.260

Gnomad NFE exome

AF:

0.261

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.258

AC:

377084

AN:

1460390

Hom.:

50294

Cov.:

AF XY:

0.254

AC XY:

184474

AN XY:

726586

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.233

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.164

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.273

Gnomad4 OTH exome

AF:

0.244

GnomAD4 genome

AF:

0.260

AC:

39565

AN:

152172

Hom.:

5213

Cov.:

AF XY:

0.255

AC XY:

19006

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.288

Gnomad4 AMR

AF:

0.241

Gnomad4 ASJ

AF:

0.111

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.167

Gnomad4 FIN

AF:

0.258

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.221

Alfa

AF:

0.249

Hom.:

1660

Bravo

AF:

0.262

Asia WGS

AF:

0.214

AC:

744

AN:

3478

EpiCase

AF:

0.240

EpiControl

AF:

0.233

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29886133) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.69

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over