Genetic Variant CNGB3:p.Gln70Glu (chr8-86739658-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_019098.5(CNGB3):c.208C>G(p.Gln70Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,406,450 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.306

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: G2P, Labcorp Genetics (formerly Invitae)
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:

CNGB3-AS1 (HGNC:58258):

CNGB3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09292558).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019098.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	NM_019098.5	MANE Select	c.208C>G	p.Gln70Glu	missense	Exon 2 of 18	NP_061971.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CNGB3	ENST00000320005.6	TSL:1 MANE Select	c.208C>G	p.Gln70Glu	missense	Exon 2 of 18	ENSP00000316605.5	Q9NQW8-1
CNGB3	ENST00000519777.1	TSL:2	n.190C>G		non_coding_transcript_exon	Exon 2 of 4
CNGB3	ENST00000681746.1		n.208C>G		non_coding_transcript_exon	Exon 2 of 19	ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000421

AC:

AN:

237748

AF XY:

0.00000776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000927

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000149

AC:

AN:

1406450

Hom.:

Cov.:

AF XY:

0.0000129

AC XY:

AN XY:

699764

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31398

American (AMR)

AF:

0.00

AC:

AN:

41670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24990

East Asian (EAS)

AF:

0.00

AC:

AN:

37692

South Asian (SAS)

AF:

0.00

AC:

AN:

81890

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5552

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1074384

Other (OTH)

AF:

0.00

AC:

AN:

57858

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

9.0

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.060

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.50

M_CAP

Benign

0.0045

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.31

PrimateAI

Benign

0.30

PROVEAN

Benign

0.68

REVEL

Benign

0.047

Sift

Benign

0.36

Sift4G

Benign

1.0

Polyphen

0.30

Vest4

0.23

MutPred

0.10

Gain of ubiquitination at K75 (P = 0.0668)

MVP

0.37

MPC

0.028

ClinPred

0.070

GERP RS

2.9

Varity_R

0.042

gMVP

0.17

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over