rs7307229

Variant names:

• chr12-6534437-C-G
• rs7307229
• NM_002046.7:c.-156C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002046.7(GAPDH):​c.-156C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 320,268 control chromosomes in the GnomAD database, including 1,079 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 0.067 (1009 hom., cov: 33)
  • Exomes 𝑓: 0.012 (70 hom.)
• Consequence: GAPDH NM_002046.7 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 2 publications found

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-DT (HGNC:55492): (GAPDH divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	NM_002046.7	MANE Select	c.-156C>G		upstream_gene	N/A	NP_002037.2
	GAPDH	NM_001289745.3		c.-248C>G		upstream_gene	N/A	NP_001276674.1
	GAPDH	NM_001289746.2		c.-396C>G		upstream_gene	N/A	NP_001276675.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	ENST00000229239.10	TSL:1 MANE Select	c.-156C>G		upstream_gene	N/A	ENSP00000229239.5
	GAPDH	ENST00000396861.5	TSL:5	c.-248C>G		upstream_gene	N/A	ENSP00000380070.1
	GAPDH	ENST00000396856.5	TSL:5	c.-408C>G		upstream_gene	N/A	ENSP00000380065.1

Frequencies

GnomAD3 genomes AF: 0.0665 AC: 10099 AN: 151936 Hom.: 999 Cov.: 33

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.000974

Gnomad SAS AF: 0.0451

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00284

Gnomad OTH AF: 0.0468

GnomAD4 exome AF: 0.0124 AC: 2085 AN: 168206 Hom.: 70 Cov.: 0 AF XY: 0.0162 AC XY: 1515 AN XY: 93740

African (AFR) AF: 0.144 AC: 185 AN: 1284

American (AMR) AF: 0.0124 AC: 62 AN: 5000

Ashkenazi Jewish (ASJ) AF: 0.00884 AC: 31 AN: 3506

East Asian (EAS) AF: 0.000260 AC: 1 AN: 3842

South Asian (SAS) AF: 0.0400 AC: 1469 AN: 36692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9220

Middle Eastern (MID) AF: 0.0247 AC: 15 AN: 608

European-Non Finnish (NFE) AF: 0.00205 AC: 204 AN: 99596

Other (OTH) AF: 0.0140 AC: 118 AN: 8458

GnomAD4 genome AF: 0.0667 AC: 10146 AN: 152062 Hom.: 1009 Cov.: 33 AF XY: 0.0655 AC XY: 4869 AN XY: 74354

African (AFR) AF: 0.220 AC: 9120 AN: 41490

American (AMR) AF: 0.0303 AC: 463 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3472

East Asian (EAS) AF: 0.000976 AC: 5 AN: 5124

South Asian (SAS) AF: 0.0451 AC: 215 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00284 AC: 193 AN: 67990

Other (OTH) AF: 0.0468 AC: 99 AN: 2114

Alfa AF: 0.0514 Hom.: 70

Bravo AF: 0.0748

Asia WGS AF: 0.0380 AC: 131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.36
DANN	Benign	0.69
PhyloP100		-2.1
PromoterAI		0.055	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7307229; hg19: chr12-6643603;