Genetic Variant NM_019098.5:c.211+33_211+34dupAA (chr8-86739620-G-GTT) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019098.5(CNGB3):c.211+33_211+34dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 0)

Exomes 𝑓: 0.016 ( 1 hom. )

Consequence

CNGB3
NM_019098.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.129

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:

CNGB3-AS1 (HGNC:58258):

CNGB3-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.211+33_211+34dupAA		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.211+34_211+35insAA	intron	N/A	ENSP00000316605.5	Q9NQW8-1
CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21216_449-21215insTT	intron	N/A
CNGB3	ENST00000519777.1	TSL:2	n.193+34_193+35insAA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.000411

AC:

AN:

128862

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000402

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000463

Gnomad ASJ

AF:

0.000637

Gnomad EAS

AF:

0.000224

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000349

Gnomad OTH

AF:

0.000571

GnomAD4 exome

AF:

0.0165

AC:

21945

AN:

1330878

Hom.:

Cov.:

AF XY:

0.0177

AC XY:

11740

AN XY:

661476

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.0337

AC:

987

AN:

29292

American (AMR)

AF:

0.0285

AC:

1051

AN:

36850

Ashkenazi Jewish (ASJ)

AF:

0.0300

AC:

704

AN:

23446

East Asian (EAS)

AF:

0.0181

AC:

665

AN:

36714

South Asian (SAS)

AF:

0.0446

AC:

3271

AN:

73364

European-Finnish (FIN)

AF:

0.0199

AC:

828

AN:

41696

Middle Eastern (MID)

AF:

0.0161

AC:

AN:

5166

European-Non Finnish (NFE)

AF:

0.0130

AC:

13380

AN:

1029350

Other (OTH)

AF:

0.0177

AC:

976

AN:

55000

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.291

Heterozygous variant carriers

1849

3698

5547

7396

9245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

276

552

828

1104

1380

<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:

0.000411

AC:

AN:

128872

Hom.:

Cov.:

AF XY:

0.000356

AC XY:

AN XY:

61814

show subpopulations

African (AFR)

AF:

0.000402

AC:

AN:

34864

American (AMR)

AF:

0.000463

AC:

AN:

12968

Ashkenazi Jewish (ASJ)

AF:

0.000637

AC:

AN:

3140

East Asian (EAS)

AF:

0.000225

AC:

AN:

4452

South Asian (SAS)

AF:

0.00

AC:

AN:

3990

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

6438

Middle Eastern (MID)

AF:

0.00

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.000349

AC:

AN:

60190

Other (OTH)

AF:

0.000568

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.405

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0306

Hom.:

244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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