11-67452544-C-T

Position:

• chr11-67452544-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 12/20 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.38

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]

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR152	NM_206997.1	c.181G>A	p.Gly61Arg	missense_variant	1/1	ENST00000312457.2	NP_996880.1
CABP4	NM_001300896.3	c.-215C>T		5_prime_UTR_variant	1/7		NP_001287825.1
CABP4	NM_001379183.1	c.-611C>T		5_prime_UTR_variant	1/9		NP_001366112.1
CABP4	XM_024448615.2	c.-2789C>T		5_prime_UTR_variant	1/7		XP_024304383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR152	ENST00000312457.2	c.181G>A	p.Gly61Arg	missense_variant	1/1	6	NM_206997.1	ENSP00000310255.2

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 1638 AN: 152224 Hom.: 92 Cov.: 33

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

GnomAD3 exomes AF: 0.0194 AC: 4460 AN: 229754 Hom.: 324 AF XY: 0.0176 AC XY: 2215 AN XY: 125548

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 SAS exome AF: 0.00343

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.: 32 AF XY: 0.00748 AC XY: 5406 AN XY: 722972

Gnomad4 AFR exome AF: 0.000750

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.00274

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.00385

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.000473

Gnomad4 OTH exome AF: 0.0103

GnomAD4 genome AF: 0.0108 AC: 1645 AN: 152344 Hom.: 93 Cov.: 33 AF XY: 0.0133 AC XY: 993 AN XY: 74498

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.0112

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0289

Gnomad4 NFE AF: 0.00116

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00802 Hom.: 102

Bravo AF: 0.0105

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.000932 AC: 8

ExAC AF: 0.0167 AC: 2017

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Cone-rod synaptic disorder, congenital nonprogressive Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.42	N
MutationTaster	Benign	0.77	P;P
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.13
Sift	Benign	0.099	T
Sift4G	Benign	0.20	T
Polyphen		0.42	B
Vest4		0.10
MutPred		0.56		Loss of catalytic residue at G61 (P = 0.0172);
MPC		0.89
ClinPred		0.027	T
GERP RS		4.0
Varity_R		0.070
gMVP		0.37

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: rs79423227; hg19: chr11-67220015; COSMIC: COSV56887564; COSMIC: COSV56887564;