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GeneBe

7-1057959-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001303473.2(GPR146):c.444C>T(p.Cys148=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 771,994 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0091 ( 11 hom., cov: 33)
Exomes 𝑓: 0.0091 ( 48 hom. )

Consequence

GPR146
NM_001303473.2 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.283
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 -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-1057959-C-T is Benign according to our data. Variant chr7-1057959-C-T is described in ClinVar as [Benign]. Clinvar id is 773473.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.283 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GPR146NM_001303473.2 linkuse as main transcriptc.444C>T p.Cys148= synonymous_variant 2/2 ENST00000444847.2
C7orf50NM_001318252.2 linkuse as main transcriptc.130-47816G>A intron_variant ENST00000397098.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GPR146ENST00000444847.2 linkuse as main transcriptc.444C>T p.Cys148= synonymous_variant 2/22 NM_001303473.2 P1
C7orf50ENST00000397098.8 linkuse as main transcriptc.130-47816G>A intron_variant 1 NM_001318252.2 P1
ENST00000549241.1 linkuse as main transcriptn.1303G>A non_coding_transcript_exon_variant 1/24

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00914
AC:
1391
AN:
152240
Hom.:
11
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00200
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.00713
Gnomad ASJ
AF:
0.00432
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00165
Gnomad FIN
AF:
0.0339
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.0116
Gnomad OTH
AF:
0.0110
GnomAD3 exomes
AF:
0.00807
AC:
1973
AN:
244576
Hom.:
17
AF XY:
0.00837
AC XY:
1113
AN XY:
132986
show subpopulations
Gnomad AFR exome
AF:
0.00167
Gnomad AMR exome
AF:
0.00602
Gnomad ASJ exome
AF:
0.00209
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.00114
Gnomad FIN exome
AF:
0.0295
Gnomad NFE exome
AF:
0.0102
Gnomad OTH exome
AF:
0.0107
GnomAD4 exome
AF:
0.00912
AC:
5648
AN:
619636
Hom.:
48
Cov.:
0
AF XY:
0.00889
AC XY:
3009
AN XY:
338408
show subpopulations
Gnomad4 AFR exome
AF:
0.00198
Gnomad4 AMR exome
AF:
0.00601
Gnomad4 ASJ exome
AF:
0.00262
Gnomad4 EAS exome
AF:
0.0000555
Gnomad4 SAS exome
AF:
0.00132
Gnomad4 FIN exome
AF:
0.0278
Gnomad4 NFE exome
AF:
0.0104
Gnomad4 OTH exome
AF:
0.00935
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00913
AC:
1391
AN:
152358
Hom.:
11
Cov.:
33
AF XY:
0.0102
AC XY:
761
AN XY:
74510
show subpopulations
Gnomad4 AFR
AF:
0.00200
Gnomad4 AMR
AF:
0.00712
Gnomad4 ASJ
AF:
0.00432
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.0339
Gnomad4 NFE
AF:
0.0116
Gnomad4 OTH
AF:
0.0109
Alfa
AF:
0.00896
Hom.:
3
Bravo
AF:
0.00666
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
0.85
Dann
Benign
0.84
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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: rs142752160; hg19: chr7-1097595; COSMIC: COSV99866313; COSMIC: COSV99866313; API