7-1057919-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001303473.2(GPR146):​c.404G>A​(p.Arg135Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 774,898 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0018 ( 11 hom. )

Consequence

GPR146
NM_001303473.2 missense

Scores

2
8
9

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 9.21
Variant links:
Genes affected
GPR146 (HGNC:21718): (G protein-coupled receptor 146) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
C7orf50 (HGNC:22421): (chromosome 7 open reading frame 50) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013405383).
BP6
Variant 7-1057919-G-A is Benign according to our data. Variant chr7-1057919-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657177.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GPR146NM_001303473.2 linkuse as main transcriptc.404G>A p.Arg135Gln missense_variant 2/2 ENST00000444847.2 NP_001290402.1
C7orf50NM_001318252.2 linkuse as main transcriptc.130-47776C>T intron_variant ENST00000397098.8 NP_001305181.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GPR146ENST00000444847.2 linkuse as main transcriptc.404G>A p.Arg135Gln missense_variant 2/22 NM_001303473.2 ENSP00000410743 P1
C7orf50ENST00000397098.8 linkuse as main transcriptc.130-47776C>T intron_variant 1 NM_001318252.2 ENSP00000380286 P1
ENST00000549241.1 linkuse as main transcriptn.1343C>T non_coding_transcript_exon_variant 1/24

Frequencies

GnomAD3 genomes
AF:
0.00108
AC:
165
AN:
152228
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000338
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000719
Gnomad ASJ
AF:
0.00432
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00455
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.00131
Gnomad OTH
AF:
0.00383
GnomAD3 exomes
AF:
0.00171
AC:
422
AN:
246410
Hom.:
3
AF XY:
0.00215
AC XY:
288
AN XY:
133852
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000781
Gnomad ASJ exome
AF:
0.00358
Gnomad EAS exome
AF:
0.000164
Gnomad SAS exome
AF:
0.00549
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00156
Gnomad OTH exome
AF:
0.00164
GnomAD4 exome
AF:
0.00184
AC:
1146
AN:
622552
Hom.:
11
Cov.:
0
AF XY:
0.00220
AC XY:
747
AN XY:
339782
show subpopulations
Gnomad4 AFR exome
AF:
0.000396
Gnomad4 AMR exome
AF:
0.000846
Gnomad4 ASJ exome
AF:
0.00334
Gnomad4 EAS exome
AF:
0.0000555
Gnomad4 SAS exome
AF:
0.00559
Gnomad4 FIN exome
AF:
0.0000212
Gnomad4 NFE exome
AF:
0.00150
Gnomad4 OTH exome
AF:
0.00266
GnomAD4 genome
AF:
0.00108
AC:
165
AN:
152346
Hom.:
0
Cov.:
33
AF XY:
0.00102
AC XY:
76
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000337
Gnomad4 AMR
AF:
0.000718
Gnomad4 ASJ
AF:
0.00432
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00456
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00131
Gnomad4 OTH
AF:
0.00379
Alfa
AF:
0.00151
Hom.:
1
Bravo
AF:
0.000948
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.00104
AC:
4
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00186
AC:
16
ExAC
AF:
0.00170
AC:
206
Asia WGS
AF:
0.00375
AC:
13
AN:
3478
EpiCase
AF:
0.00344
EpiControl
AF:
0.00231

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenOct 01, 2022GPR146: BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.050
.;T
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.013
T;T
MetaSVM
Benign
-0.99
T
MutationAssessor
Uncertain
2.1
.;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-1.8
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.045
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
.;D
Vest4
0.90
MVP
0.53
MPC
0.46
ClinPred
0.040
T
GERP RS
5.1
Varity_R
0.30
gMVP
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61997249; hg19: chr7-1097555; API