X-16128998-G-A

Position:

• chrX-16128998-G-A

Variant summary

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

The NM_005314.3(GRPR):​c.413+4632G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.097 in 111,528 control chromosomes in the GnomAD database, including 1,305 homozygotes. There are 2,917 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 0.097 (1305 hom., 2917 hem., cov: 23)
• Consequence: GRPR NM_005314.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRPR	NM_005314.3	c.413+4632G>A		intron_variant		ENST00000380289.3	NP_005305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRPR	ENST00000380289.3	c.413+4632G>A		intron_variant		1	NM_005314.3	ENSP00000369643	P1

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 10785 AN: 111471 Hom.: 1303 Cov.: 23 AF XY: 0.0859 AC XY: 2895 AN XY: 33707

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0412

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.000165

Gnomad MID AF: 0.0433

Gnomad NFE AF: 0.00134

Gnomad OTH AF: 0.0757

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0970 AC: 10815 AN: 111528 Hom.: 1305 Cov.: 23 AF XY: 0.0864 AC XY: 2917 AN XY: 33772

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.0411

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000281

Gnomad4 SAS AF: 0.0171

Gnomad4 FIN AF: 0.000165

Gnomad4 NFE AF: 0.00134

Gnomad4 OTH AF: 0.0748

Alfa AF: 0.0303 Hom.: 877

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.29

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: rs10218163; hg19: chrX-16147121;