Genetic Variant GRTP1:c.341-1062G>C (chr13-113352035-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001286732.2(GRTP1):c.341-1062G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 150,566 control chromosomes in the GnomAD database, including 9,247 homozygotes. 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 0.34 ( 9247 hom., cov: 28)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

GRTP1
NM_001286732.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.79

Publications

4 publications found

Variant links:

Genes affected

GRTP1 (HGNC:20310): (growth hormone regulated TBC protein 1) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. [provided by Alliance of Genome Resources, Apr 2022]

GRTP1 links:

GRTP1-AS1 (HGNC:39917): (GRTP1 antisense RNA 1)

GRTP1-AS1 links:

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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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286732.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GRTP1	NM_024719.4	MANE Select	c.341-1062G>C	intron	N/A	NP_078995.2
GRTP1	NM_001286732.2		c.341-1062G>C	intron	N/A	NP_001273661.1
GRTP1	NM_001411029.1		c.107-1062G>C	intron	N/A	NP_001397958.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GRTP1	ENST00000375431.9	TSL:1 MANE Select	c.341-1062G>C	intron	N/A	ENSP00000364580.3
GRTP1	ENST00000375430.8	TSL:1	c.341-1062G>C	intron	N/A	ENSP00000364579.4
GRTP1	ENST00000326039.3	TSL:1	c.107-1062G>C	intron	N/A	ENSP00000321850.3

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

50997

AN:

150460

Hom.:

9228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.405

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.354

Gnomad FIN

AF:

0.244

Gnomad MID

AF:

0.311

Gnomad NFE

AF:

0.284

Gnomad OTH

AF:

0.311

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.339

AC:

51067

AN:

150564

Hom.:

9247

Cov.:

AF XY:

0.340

AC XY:

24979

AN XY:

73426

show subpopulations

African (AFR)

AF:

0.406

AC:

16616

AN:

40970

American (AMR)

AF:

0.421

AC:

6329

AN:

15048

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

794

AN:

3470

East Asian (EAS)

AF:

0.599

AC:

3036

AN:

5072

South Asian (SAS)

AF:

0.355

AC:

1701

AN:

4792

European-Finnish (FIN)

AF:

0.244

AC:

2476

AN:

10140

Middle Eastern (MID)

AF:

0.293

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.284

AC:

19231

AN:

67790

Other (OTH)

AF:

0.318

AC:

662

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1644

3289

4933

6578

8222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.165

Hom.:

313

Bravo

AF:

0.363

Asia WGS

AF:

0.471

AC:

1637

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.26

(source)

DANN

Benign

0.44

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over