rs3747411

Positions:

• chrX-16152954-T-A

Variant summary

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

The NM_005314.3(GRPR):​c.*309T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 315,016 control chromosomes in the GnomAD database, including 8,687 homozygotes. There are 22,583 hemizygotes in GnomAD. 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 0.23 (2581 hom., 7573 hem., cov: 23)
  • Exomes 𝑓: 0.28 (6106 hom. 15010 hem.)
• Consequence: GRPR NM_005314.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.39

Genes affected

GRPR (HGNC:4609): (gastrin releasing peptide receptor) Gastrin-releasing peptide (GRP) regulates numerous functions of the gastrointestinal and central nervous systems, including release of gastrointestinal hormones, smooth muscle cell contraction, and epithelial cell proliferation and is a potent mitogen for neoplastic tissues. The effects of GRP are mediated through the gastrin-releasing peptide receptor. This receptor is a glycosylated, 7-transmembrane G-protein coupled receptor that activates the phospholipase C signaling pathway. The receptor is aberrantly expressed in numerous cancers such as those of the lung, colon, and prostate. An individual with autism and multiple exostoses was found to have a balanced translocation between chromosome 8 and a chromosome X breakpoint located within the gastrin-releasing peptide receptor gene. [provided by RefSeq, Jul 2008]

MAGEB17-AS1 (HGNC:56739): (MAGEB17 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRPR	NM_005314.3	c.*309T>A		3_prime_UTR_variant	3/3	ENST00000380289.3	NP_005305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRPR	ENST00000380289.3	c.*309T>A		3_prime_UTR_variant	3/3	1	NM_005314.3	ENSP00000369643	P1
MAGEB17-AS1	ENST00000422438.5	n.379A>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.230 AC: 25769 AN: 111961 Hom.: 2584 Cov.: 23 AF XY: 0.222 AC XY: 7568 AN XY: 34141

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.313

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.235

GnomAD4 exome AF: 0.278 AC: 56456 AN: 203001 Hom.: 6106 Cov.: 0 AF XY: 0.290 AC XY: 15010 AN XY: 51791

Gnomad4 AFR exome AF: 0.0829

Gnomad4 AMR exome AF: 0.326

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.213

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.276

GnomAD4 genome AF: 0.230 AC: 25756 AN: 112015 Hom.: 2581 Cov.: 23 AF XY: 0.221 AC XY: 7573 AN XY: 34205

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.233

Alfa AF: 0.252 Hom.: 1579

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.71

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: rs3747411; hg19: chrX-16171077;