8-86629043-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_019098.5(CNGB3):​c.1356G>A​(p.Gln452Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00965 in 1,613,948 control chromosomes in the GnomAD database, including 1,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 677 hom., cov: 32)
Exomes 𝑓: 0.0053 ( 595 hom. )

Consequence

CNGB3
NM_019098.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.09
Variant links:
Genes affected
CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 8-86629043-C-T is Benign according to our data. Variant chr8-86629043-C-T is described in ClinVar as [Benign]. Clinvar id is 261082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-86629043-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.09 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CNGB3NM_019098.5 linkc.1356G>A p.Gln452Gln synonymous_variant Exon 12 of 18 ENST00000320005.6 NP_061971.3 Q9NQW8-1
CNGB3XM_011517138.3 linkc.942G>A p.Gln314Gln synonymous_variant Exon 10 of 16 XP_011515440.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CNGB3ENST00000320005.6 linkc.1356G>A p.Gln452Gln synonymous_variant Exon 12 of 18 1 NM_019098.5 ENSP00000316605.5 Q9NQW8-1
CNGB3ENST00000681546.1 linkn.1176G>A non_coding_transcript_exon_variant Exon 7 of 13
CNGB3ENST00000681746.1 linkn.1356G>A non_coding_transcript_exon_variant Exon 12 of 19 ENSP00000505959.1 A0A5J6DSN8

Frequencies

GnomAD3 genomes
AF:
0.0514
AC:
7810
AN:
152076
Hom.:
675
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.177
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0222
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0158
Gnomad NFE
AF:
0.000441
Gnomad OTH
AF:
0.0478
GnomAD3 exomes
AF:
0.0139
AC:
3492
AN:
250978
Hom.:
269
AF XY:
0.0103
AC XY:
1397
AN XY:
135606
show subpopulations
Gnomad AFR exome
AF:
0.185
Gnomad AMR exome
AF:
0.0111
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000415
Gnomad OTH exome
AF:
0.00833
GnomAD4 exome
AF:
0.00529
AC:
7738
AN:
1461752
Hom.:
595
Cov.:
32
AF XY:
0.00454
AC XY:
3301
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.182
Gnomad4 AMR exome
AF:
0.0117
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000325
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000332
Gnomad4 OTH exome
AF:
0.0115
GnomAD4 genome
AF:
0.0515
AC:
7837
AN:
152196
Hom.:
677
Cov.:
32
AF XY:
0.0489
AC XY:
3643
AN XY:
74436
show subpopulations
Gnomad4 AFR
AF:
0.177
Gnomad4 AMR
AF:
0.0221
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000441
Gnomad4 OTH
AF:
0.0473
Alfa
AF:
0.0275
Hom.:
143
Bravo
AF:
0.0588
Asia WGS
AF:
0.0120
AC:
44
AN:
3476
EpiCase
AF:
0.000545
EpiControl
AF:
0.000889

ClinVar

Significance: Benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:3
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Jul 05, 2018
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Achromatopsia Benign:1
Dec 02, 2019
Natera, Inc.
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

Severe early-childhood-onset retinal dystrophy Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Achromatopsia 3 Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.33
CADD
Benign
5.8
DANN
Benign
0.60

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: rs34839859; hg19: chr8-87641271; API