rs7971637

Variant names:

• chr12-6534163-C-T
• rs7971637
• ENST00000920777.1:c.-169C>T

Variant summary

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

The ENST00000920777.1(GAPDH):​c.-169C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 154,472 control chromosomes in the GnomAD database, including 2,504 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 0.17 (2469 hom., cov: 33)
  • Exomes 𝑓: 0.13 (35 hom.)
• Consequence: GAPDH ENST00000920777.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.923
• Publications: 12 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000920777.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GAPDH	ENST00000920777.1		c.-169C>T		5_prime_UTR	Exon 1 of 9	ENSP00000590836.1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26325 AN: 152050 Hom.: 2472 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.0848

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.164

GnomAD4 exome AF: 0.135 AC: 310 AN: 2304 Hom.: 35 Cov.: 0 AF XY: 0.126 AC XY: 185 AN XY: 1472

African (AFR) AF: 0.167 AC: 2 AN: 12

American (AMR) AF: 0.134 AC: 22 AN: 164

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 1 AN: 10

East Asian (EAS) AF: 0.136 AC: 3 AN: 22

South Asian (SAS) AF: 0.0781 AC: 42 AN: 538

European-Finnish (FIN) AF: 0.192 AC: 10 AN: 52

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 12

European-Non Finnish (NFE) AF: 0.156 AC: 218 AN: 1400

Other (OTH) AF: 0.128 AC: 12 AN: 94

GnomAD4 genome AF: 0.173 AC: 26327 AN: 152168 Hom.: 2469 Cov.: 33 AF XY: 0.173 AC XY: 12865 AN XY: 74412

African (AFR) AF: 0.114 AC: 4743 AN: 41536

American (AMR) AF: 0.200 AC: 3066 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0848 AC: 294 AN: 3468

East Asian (EAS) AF: 0.307 AC: 1585 AN: 5166

South Asian (SAS) AF: 0.123 AC: 594 AN: 4826

European-Finnish (FIN) AF: 0.207 AC: 2193 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13259 AN: 67962

Other (OTH) AF: 0.162 AC: 341 AN: 2110

Alfa AF: 0.184 Hom.: 1406

Bravo AF: 0.173

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.84
PhyloP100		0.92
PromoterAI		0.0074	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: rs7971637; hg19: chr12-6643329;