rs41466745

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.2103+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 1,611,896 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 337 hom., cov: 32)

Exomes 𝑓: 0.0066 ( 341 hom. )

Consequence

CNGB3
NM_019098.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.316

Publications

2 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_019098.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 8-86578666-G-C is Benign according to our data. Variant chr8-86578666-G-C is described in ClinVar as Benign. ClinVar VariationId is 261085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 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.2103+23C>G		intron	N/A	NP_061971.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGB3	ENST00000320005.6	TSL:1 MANE Select	c.2103+23C>G	intron	N/A	ENSP00000316605.5	Q9NQW8-1
CNGB3	ENST00000517327.5	TSL:3	c.276+23C>G	intron	N/A	ENSP00000428329.1	H0YAZ4
CNGB3	ENST00000681546.1		n.1923+23C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0393

AC:

5977

AN:

152084

Hom.:

333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0200

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0133

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0134

AC:

3351

AN:

250902

AF XY:

0.0113

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.0246

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.000740

Gnomad NFE exome

AF:

0.00217

Gnomad OTH exome

AF:

0.00996

GnomAD4 exome

AF:

0.00658

AC:

9612

AN:

1459694

Hom.:

341

Cov.:

AF XY:

0.00644

AC XY:

4677

AN XY:

726254

show subpopulations

African (AFR)

AF:

0.129

AC:

4317

AN:

33398

American (AMR)

AF:

0.0110

AC:

492

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0250

AC:

654

AN:

26122

East Asian (EAS)

AF:

0.000126

AC:

AN:

39682

South Asian (SAS)

AF:

0.0131

AC:

1131

AN:

86182

European-Finnish (FIN)

AF:

0.000750

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5048

European-Non Finnish (NFE)

AF:

0.00185

AC:

2051

AN:

1110926

Other (OTH)

AF:

0.0140

AC:

842

AN:

60254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

469

938

1407

1876

2345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

368

552

736

920

<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:

0.0394

AC:

5997

AN:

152202

Hom.:

337

Cov.:

AF XY:

0.0385

AC XY:

2867

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.127

AC:

5268

AN:

41526

American (AMR)

AF:

0.0200

AC:

306

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3472

East Asian (EAS)

AF:

0.00136

AC:

AN:

5164

South Asian (SAS)

AF:

0.0133

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00238

AC:

162

AN:

68018

Other (OTH)

AF:

0.0417

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

279

559

838

1118

1397

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.00524

Hom.:

Bravo

AF:

0.0444

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.55

PhyloP100

-0.32

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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