NM_002046.7:c.-8C>G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

24 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002046.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GAPDH	NM_002046.7	MANE Select	c.-8C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_002037.2
GAPDH	NM_002046.7	MANE Select	c.-8C>G	5_prime_UTR	Exon 2 of 9	NP_002037.2
GAPDH	NM_001289745.3		c.-8C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_001276674.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GAPDH	ENST00000229239.10	TSL:1 MANE Select	c.-8C>G	5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000229239.5
GAPDH	ENST00000396859.5	TSL:1	c.-8C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000380068.1
GAPDH	ENST00000229239.10	TSL:1 MANE Select	c.-8C>G	5_prime_UTR	Exon 2 of 9	ENSP00000229239.5

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

GnomAD2 exomes

AF:

0.237

AC:

59104

AN:

248998

AF XY:

0.232

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 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

African (AFR)

AF:

0.284

AC:

9506

AN:

33422

American (AMR)

AF:

0.233

AC:

10408

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3004

AN:

26114

East Asian (EAS)

AF:

0.192

AC:

7630

AN:

39652

South Asian (SAS)

AF:

0.164

AC:

14120

AN:

86236

European-Finnish (FIN)

AF:

0.264

AC:

14063

AN:

53182

Middle Eastern (MID)

AF:

0.104

AC:

590

AN:

5674

European-Non Finnish (NFE)

AF:

0.273

AC:

303063

AN:

1111058

Other (OTH)

AF:

0.244

AC:

14700

AN:

60342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

13901

27801

41702

55602

69503

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10140

20280

30420

40560

50700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.260

AC:

39565

AN:

152172

Hom.:

5213

Cov.:

AF XY:

0.255

AC XY:

19006

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.288

AC:

11936

AN:

41504

American (AMR)

AF:

0.241

AC:

3691

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.111

AC:

387

AN:

3472

East Asian (EAS)

AF:

0.220

AC:

1141

AN:

5180

South Asian (SAS)

AF:

0.167

AC:

805

AN:

4834

European-Finnish (FIN)

AF:

0.258

AC:

2738

AN:

10594

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.268

AC:

18187

AN:

67978

Other (OTH)

AF:

0.221

AC:

466

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1534

3068

4602

6136

7670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

402

804

1206

1608

2010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.21

PromoterAI

0.0079

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over