Genetic Variant CNGB3:c.211+32_211+34dupAAA (chr8-86739620-G-GTTT) – 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+32_211+34dupAAA 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 0.000031 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0019 ( 0 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:

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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+32_211+34dupAAA		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+35insAAA	intron	N/A	ENSP00000316605.5	Q9NQW8-1
CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21216_449-21215insTTT	intron	N/A
CNGB3	ENST00000519777.1	TSL:2	n.193+34_193+35insAAA	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000310

AC:

AN:

128882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000287

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000772

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000332

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00185

AC:

2507

AN:

1354566

Hom.:

Cov.:

AF XY:

0.00200

AC XY:

1349

AN XY:

673372

show subpopulations

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

African (AFR)

AF:

0.00439

AC:

131

AN:

29840

American (AMR)

AF:

0.00413

AC:

155

AN:

37568

Ashkenazi Jewish (ASJ)

AF:

0.00376

AC:

AN:

23968

East Asian (EAS)

AF:

0.00204

AC:

AN:

37300

South Asian (SAS)

AF:

0.00628

AC:

475

AN:

75664

European-Finnish (FIN)

AF:

0.00266

AC:

113

AN:

42408

Middle Eastern (MID)

AF:

0.00152

AC:

AN:

5254

European-Non Finnish (NFE)

AF:

0.00127

AC:

1333

AN:

1046574

Other (OTH)

AF:

0.00225

AC:

126

AN:

55990

⚠️ 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: 0.297

Heterozygous variant carriers

217

434

650

867

1084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.0000310

AC:

AN:

128892

Hom.:

Cov.:

AF XY:

0.0000162

AC XY:

AN XY:

61824

show subpopulations

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

African (AFR)

AF:

0.0000287

AC:

AN:

34868

American (AMR)

AF:

0.0000771

AC:

AN:

12968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3144

East Asian (EAS)

AF:

0.00

AC:

AN:

4452

South Asian (SAS)

AF:

0.00

AC:

AN:

3992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.0000332

AC:

AN:

60196

Other (OTH)

AF:

0.00

AC:

AN:

1762

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000164189), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.362

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00740

Hom.:

244

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.13

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over