Genetic Variant NM_005314.3:c.*309T>A (chrX-16152954-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.39

Publications

2 publications found

Variant links:

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]

GRPR links:

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

MAGEB17-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRPR	NM_005314.3 link	c.*309T>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000380289.3	NP_005305.1	P30550X5D7H2
MAGEB17-AS1	NR_187144.1 link	n.*146A>T		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRPR	ENST00000380289.3 link	c.*309T>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_005314.3	ENSP00000369643.2		P30550

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

25769

AN:

111961

Hom.:

2584

Cov.:

show subpopulations

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.:

AF XY:

0.290

AC XY:

15010

AN XY:

51791

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1389

2778

4167

5556

6945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.230

AC:

25756

AN:

112015

Hom.:

2581

Cov.:

AF XY:

0.221

AC XY:

7573

AN XY:

34205

show subpopulations

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:

AN:

216

European-Non Finnish (NFE)

AF:

0.301

AC:

15952

AN:

53033

Other (OTH)

AF:

0.233

AC:

361

AN:

1547

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

699

1399

2098

2798

3497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.71

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over