rs311497

Positions:

• chr20-63589896-A-G
• chr20-63589896-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012384.5(GMEB2):​c.*193T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.536 in 431,982 control chromosomes in the GnomAD database, including 65,439 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 0.52 (21385 hom., cov: 34)
  • Exomes 𝑓: 0.54 (44054 hom.)
• Consequence: GMEB2 NM_012384.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.506

Genes affected

GMEB2 (HGNC:4371): (glucocorticoid modulatory element binding protein 2) This gene is a member of KDWK gene family. The product of this gene associates with GMEB1 protein, and the complex is essential for parvovirus DNA replication. Study of rat homolog implicates the role of this gene in modulation of transactivation by the glucocorticoid receptor bound to glucocorticoid response elements. This gene appears to use multiple polyadenylation sites. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GMEB2	NM_012384.5	c.*193T>C		3_prime_UTR_variant	10/10	ENST00000370077.2	NP_036516.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMEB2	ENST00000370077.2	c.*193T>C		3_prime_UTR_variant	10/10	1	NM_012384.5	ENSP00000359094.1
GMEB2	ENST00000266068.5	c.*193T>C		3_prime_UTR_variant	9/9	2		ENSP00000266068.1
GMEB2	ENST00000370069.5	c.*193T>C		3_prime_UTR_variant	8/8	5		ENSP00000359086.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79026 AN: 152016 Hom.: 21386 Cov.: 34

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.545 AC: 152473 AN: 279848 Hom.: 44054 Cov.: 4 AF XY: 0.546 AC XY: 78306 AN XY: 143348

Gnomad4 AFR exome AF: 0.428

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.668

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.351

Gnomad4 FIN exome AF: 0.524

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.546

GnomAD4 genome AF: 0.520 AC: 79050 AN: 152134 Hom.: 21385 Cov.: 34 AF XY: 0.512 AC XY: 38055 AN XY: 74376

Gnomad4 AFR AF: 0.429

Gnomad4 AMR AF: 0.538

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.546

Alfa AF: 0.586 Hom.: 54470

Bravo AF: 0.518

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.40

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

Other links and lift over

dbSNP: rs311497; hg19: chr20-62221249; COSMIC: COSV56605590;