rs3747411

Variant names:

• chrX-16152954-T-A
• rs3747411
• NM_005314.3:c.*309T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005314.3. 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
	GRPR	NM_005314.3	MANE Select	c.*309T>A		3_prime_UTR	Exon 3 of 3	NP_005305.1
	MAGEB17-AS1	NR_187144.1		n.*146A>T		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRPR	ENST00000380289.3	TSL:1 MANE Select	c.*309T>A		3_prime_UTR	Exon 3 of 3	ENSP00000369643.2
	MAGEB17-AS1	ENST00000422438.5	TSL:3	n.379A>T		non_coding_transcript_exon	Exon 4 of 4
	MAGEB17-AS1	ENST00000454712.8	TSL:3	n.*136A>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.230 AC: 25769 AN: 111961 Hom.: 2584 Cov.: 23

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

African (AFR) AF: 0.0829 AC: 599 AN: 7225

American (AMR) AF: 0.326 AC: 3302 AN: 10131

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1986 AN: 6282

East Asian (EAS) AF: 0.155 AC: 2155 AN: 13899

South Asian (SAS) AF: 0.213 AC: 3343 AN: 15660

European-Finnish (FIN) AF: 0.248 AC: 2891 AN: 11680

Middle Eastern (MID) AF: 0.280 AC: 245 AN: 876

European-Non Finnish (NFE) AF: 0.309 AC: 38438 AN: 124578

Other (OTH) AF: 0.276 AC: 3497 AN: 12670

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

African (AFR) AF: 0.0817 AC: 2531 AN: 30989

American (AMR) AF: 0.312 AC: 3315 AN: 10610

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 808 AN: 2635

East Asian (EAS) AF: 0.164 AC: 588 AN: 3577

South Asian (SAS) AF: 0.208 AC: 559 AN: 2688

European-Finnish (FIN) AF: 0.214 AC: 1293 AN: 6039

Middle Eastern (MID) AF: 0.282 AC: 61 AN: 216

European-Non Finnish (NFE) AF: 0.301 AC: 15952 AN: 53033

Other (OTH) AF: 0.233 AC: 361 AN: 1547

Alfa AF: 0.252 Hom.: 1579

Bravo AF: 0.232

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.9
DANN	Benign	0.71
PhyloP100		1.4
Mutation Taster		=100/0	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: rs3747411; hg19: chrX-16171077;