rs6471482

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_019098.5(CNGB3):c.702T>G(p.Cys234Trp) variant causes a missense change. The variant allele was found at a frequency of 0.857 in 1,613,820 control chromosomes in the GnomAD database, including 594,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C234S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.89 ( 60939 hom., cov: 31)

Exomes 𝑓: 0.85 ( 533812 hom. )

Consequence

CNGB3
NM_019098.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 5.03

Publications

41 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), 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.7922883E-7).

BP6

Variant 8-86667075-A-C is Benign according to our data. Variant chr8-86667075-A-C is described in ClinVar as Benign. ClinVar VariationId is 261090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

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.702T>G	p.Cys234Trp	missense	Exon 6 of 18	NP_061971.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	ENST00000320005.6	TSL:1 MANE Select	c.702T>G	p.Cys234Trp	missense	Exon 6 of 18	ENSP00000316605.5	Q9NQW8-1
	CNGB3	ENST00000681746.1		n.702T>G		non_coding_transcript_exon	Exon 6 of 19	ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes

AF:

0.893

AC:

135739

AN:

152048

Hom.:

60875

Cov.:

show subpopulations

Gnomad AFR

AF:

0.971

Gnomad AMI

AF:

0.888

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.867

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.984

Gnomad FIN

AF:

0.874

Gnomad MID

AF:

0.892

Gnomad NFE

AF:

0.832

Gnomad OTH

AF:

0.904

GnomAD2 exomes

AF:

0.892

AC:

224365

AN:

251402

AF XY:

0.893

show subpopulations

Gnomad AFR exome

AF:

0.975

Gnomad AMR exome

AF:

0.932

Gnomad ASJ exome

AF:

0.869

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.865

Gnomad NFE exome

AF:

0.835

Gnomad OTH exome

AF:

0.873

GnomAD4 exome

AF:

0.853

AC:

1246827

AN:

1461654

Hom.:

533812

Cov.:

AF XY:

0.857

AC XY:

622898

AN XY:

727124

show subpopulations

African (AFR)

AF:

0.976

AC:

32690

AN:

33480

American (AMR)

AF:

0.929

AC:

41533

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

22662

AN:

26132

East Asian (EAS)

AF:

1.00

AC:

39687

AN:

39698

South Asian (SAS)

AF:

0.982

AC:

84697

AN:

86252

European-Finnish (FIN)

AF:

0.863

AC:

46099

AN:

53418

Middle Eastern (MID)

AF:

0.931

AC:

5364

AN:

5762

European-Non Finnish (NFE)

AF:

0.829

AC:

921402

AN:

1111818

Other (OTH)

AF:

0.873

AC:

52693

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10059

20119

30178

40238

50297

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21068

42136

63204

84272

105340

<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

AF:

0.893

AC:

135864

AN:

152166

Hom.:

60939

Cov.:

AF XY:

0.897

AC XY:

66690

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.971

AC:

40319

AN:

41524

American (AMR)

AF:

0.906

AC:

13839

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

3010

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5146

AN:

5152

South Asian (SAS)

AF:

0.984

AC:

4748

AN:

4826

European-Finnish (FIN)

AF:

0.874

AC:

9257

AN:

10594

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.832

AC:

56558

AN:

68002

Other (OTH)

AF:

0.905

AC:

1916

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

737

1474

2212

2949

3686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

900

1800

2700

3600

4500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.858

Hom.:

190483

Bravo

AF:

0.899

TwinsUK

AF:

0.824

AC:

3057

ALSPAC

AF:

0.831

AC:

3202

ESP6500AA

AF:

0.967

AC:

4259

ESP6500EA

AF:

0.833

AC:

7168

ExAC

AF:

0.894

AC:

108602

Asia WGS

AF:

0.981

AC:

3411

AN:

3478

EpiCase

AF:

0.843

EpiControl

AF:

0.839

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

Achromatopsia 3 (3)

not provided (3)

Achromatopsia (1)

Severe early-childhood-onset retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.35

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.50

MetaRNN

Benign

6.8e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-3.4

PhyloP100

5.0

PrimateAI

Uncertain

0.60

PROVEAN

Benign

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.074

MPC

0.032

ClinPred

0.0094

GERP RS

5.5

Varity_R

0.34

gMVP

0.79

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over