chr11-67452544-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_206997.1(GPR152):c.181G>A(p.Gly61Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00794 in 1,606,520 control chromosomes in the GnomAD database, including 962 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0076 ( 869 hom. )

Consequence

GPR152
NM_206997.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.38

Publications

3 publications found

Variant links:

Genes affected

GPR152 (HGNC:23622): (G protein-coupled receptor 152) Enables identical protein binding activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

GPR152 links:

CABP4 (HGNC:1386): (calcium binding protein 4) This gene encodes a member of the CABP family of calcium binding protein characterized by four EF-hand motifs. Mutations in this gene are associated with congenital stationary night blindness type 2B. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

CABP4 Gene-Disease associations (from GenCC):

cone-rod synaptic disorder, congenital nonprogressive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant nocturnal frontal lobe epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CABP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016772151).

BP6

Variant 11-67452544-C-T is Benign according to our data. Variant chr11-67452544-C-T is described in ClinVar as Benign. ClinVar VariationId is 802691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206997.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR152	NM_206997.1	MANE Select	c.181G>A	p.Gly61Arg	missense	Exon 1 of 1	NP_996880.1	Q8TDT2
CABP4	NM_001300896.3		c.-215C>T		5_prime_UTR	Exon 1 of 7	NP_001287825.1	P57796-2
CABP4	NM_001379183.1		c.-611C>T		5_prime_UTR	Exon 1 of 9	NP_001366112.1	P57796-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR152	ENST00000312457.2	TSL:6 MANE Select	c.181G>A	p.Gly61Arg	missense	Exon 1 of 1	ENSP00000310255.2	Q8TDT2
CABP4	ENST00000438189.6	TSL:1	c.-215C>T		5_prime_UTR	Exon 1 of 7	ENSP00000401555.2	P57796-2
CABP4	ENST00000545040.1	TSL:1	n.109C>T		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1638

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.0289

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00116

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.0194

AC:

4460

AN:

229754

AF XY:

0.0176

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.0133

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.190

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00764

AC:

11108

AN:

1454176

Hom.:

869

Cov.:

AF XY:

0.00748

AC XY:

5406

AN XY:

722972

show subpopulations

African (AFR)

AF:

0.000750

AC:

AN:

33354

American (AMR)

AF:

0.0135

AC:

582

AN:

43170

Ashkenazi Jewish (ASJ)

AF:

0.00274

AC:

AN:

25912

East Asian (EAS)

AF:

0.199

AC:

7825

AN:

39388

South Asian (SAS)

AF:

0.00385

AC:

329

AN:

85450

European-Finnish (FIN)

AF:

0.0215

AC:

1121

AN:

52258

Middle Eastern (MID)

AF:

0.00193

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.000473

AC:

524

AN:

1108902

Other (OTH)

AF:

0.0103

AC:

620

AN:

60048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

673

1346

2018

2691

3364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<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:

0.0108

AC:

1645

AN:

152344

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

993

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41582

American (AMR)

AF:

0.0112

AC:

171

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

960

AN:

5184

South Asian (SAS)

AF:

0.00746

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0289

AC:

307

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00116

AC:

AN:

68022

Other (OTH)

AF:

0.00615

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

164

245

327

409

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00741

Hom.:

105

Bravo

AF:

0.0105

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000932

AC:

ExAC

AF:

0.0167

AC:

2017

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cone-rod synaptic disorder, congenital nonprogressive (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0027

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.42

PhyloP100

1.4

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.98

REVEL

Benign

0.13

Sift

Benign

0.099

Sift4G

Benign

0.20

Polyphen

0.42

Vest4

0.10

MutPred

0.56

Loss of catalytic residue at G61 (P = 0.0172)

MPC

0.89

ClinPred

0.027

GERP RS

4.0

PromoterAI

0.014

Neutral

(source)

Varity_R

0.070

gMVP

0.37

Mutation Taster

=97/3

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over