dbSNP rs1554619292: CNGB3:p.Glu64SerfsTer19 (chr8-86739675-TC-T) – ACMG Classification: Pathogenic (10 pts)

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PP5_Moderate

The NM_019098.5(CNGB3):c.190delG(p.Glu64SerfsTer19) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. E64E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

CNGB3
NM_019098.5 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 0.640

Publications

0 publications found

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]

CNGB3 Gene-Disease associations (from GenCC):

achromatopsia 3
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
CNGB3-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
severe early-childhood-onset retinal dystrophy
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

CNGB3 links:

ENSG00000253778 (HGNC:58258):

ENSG00000253778 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 10 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PP5

Variant 8-86739675-TC-T is Pathogenic according to our data. Variant chr8-86739675-TC-T is described in ClinVar as Pathogenic. ClinVar VariationId is 427646.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5 link	c.190delG	p.Glu64SerfsTer19	frameshift_variant	Exon 2 of 18	ENST00000320005.6	NP_061971.3	Q9NQW8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6 link	c.190delG	p.Glu64SerfsTer19	frameshift_variant	Exon 2 of 18	1	NM_019098.5	ENSP00000316605.5		Q9NQW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000548

AC:

AN:

1460582

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726662

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33462

American (AMR)

AF:

0.00

AC:

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111550

Other (OTH)

AF:

0.00

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Achromatopsia 3

Pathogenic:2

Genomics England Pilot Project, Genomics England

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 27, 2017

Molecular Genetics Laboratory, Institute for Ophthalmic Research

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:research

- -

Achromatopsia

Pathogenic:1

Mar 27, 2025

Natera, Inc.

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.64

Mutation Taster

=4/196

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over