rs10218163

Variant names:

• chrX-16128998-G-A
• rs10218163
• NM_005314.3:c.413+4632G>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.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
• Publications: 1 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]

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRPR	NM_005314.3	MANE Select	c.413+4632G>A		intron	N/A	NP_005305.1	X5D7H2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GRPR	ENST00000380289.3	TSL:1 MANE Select	c.413+4632G>A		intron	N/A	ENSP00000369643.2	P30550

Frequencies

GnomAD3 genomes AF: 0.0968 AC: 10785 AN: 111471 Hom.: 1303 Cov.: 23

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

African (AFR) AF: 0.333 AC: 10138 AN: 30464

American (AMR) AF: 0.0411 AC: 435 AN: 10579

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.000281 AC: 1 AN: 3559

South Asian (SAS) AF: 0.0171 AC: 45 AN: 2639

European-Finnish (FIN) AF: 0.000165 AC: 1 AN: 6063

Middle Eastern (MID) AF: 0.0469 AC: 10 AN: 213

European-Non Finnish (NFE) AF: 0.00134 AC: 71 AN: 53152

Other (OTH) AF: 0.0748 AC: 114 AN: 1524

Alfa AF: 0.0428 Hom.: 1947

Bravo AF: 0.112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.23
DANN	Benign	0.29
PhyloP100		0.058
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: rs10218163; hg19: chrX-16147121;