NM_019098.5:c.1179-38T>C

Variant names:

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.1179-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 1,585,200 control chromosomes in the GnomAD database, including 4,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.053 ( 292 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3953 hom. )

Consequence

CNGB3
NM_019098.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.27

Publications

3 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: Labcorp Genetics (formerly Invitae), G2P, 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 (BayesDel_noAF=-0.88).

BP6

Variant 8-86632931-A-G is Benign according to our data. Variant chr8-86632931-A-G is described in ClinVar as Benign. ClinVar VariationId is 261081.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0704 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5 link	c.1179-38T>C		intron_variant	Intron 10 of 17	ENST00000320005.6	NP_061971.3	Q9NQW8-1
CNGB3	XM_011517138.3 link	c.765-38T>C		intron_variant	Intron 8 of 15		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNGB3	ENST00000320005.6 link	c.1179-38T>C	intron_variant	Intron 10 of 17	1	NM_019098.5	ENSP00000316605.5	Q9NQW8-1
CNGB3	ENST00000681546.1 link	n.999-38T>C	intron_variant	Intron 5 of 12
CNGB3	ENST00000681746.1 link	n.1179-38T>C	intron_variant	Intron 10 of 18			ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes

AF:

0.0530

AC:

8065

AN:

152162

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0155

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0483

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.0766

Gnomad FIN

AF:

0.0954

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0536

GnomAD2 exomes

AF:

0.0661

AC:

16394

AN:

248102

AF XY:

0.0674

show subpopulations

Gnomad AFR exome

AF:

0.0133

Gnomad AMR exome

AF:

0.0663

Gnomad ASJ exome

AF:

0.0402

Gnomad EAS exome

AF:

0.0492

Gnomad FIN exome

AF:

0.0922

Gnomad NFE exome

AF:

0.0707

Gnomad OTH exome

AF:

0.0676

GnomAD4 exome

AF:

0.0718

AC:

102840

AN:

1432920

Hom.:

3953

Cov.:

AF XY:

0.0716

AC XY:

51172

AN XY:

714548

show subpopulations

African (AFR)

AF:

0.0135

AC:

441

AN:

32772

American (AMR)

AF:

0.0653

AC:

2908

AN:

44506

Ashkenazi Jewish (ASJ)

AF:

0.0397

AC:

1029

AN:

25924

East Asian (EAS)

AF:

0.0764

AC:

3010

AN:

39392

South Asian (SAS)

AF:

0.0751

AC:

6405

AN:

85296

European-Finnish (FIN)

AF:

0.0901

AC:

4800

AN:

53260

Middle Eastern (MID)

AF:

0.0318

AC:

130

AN:

4088

European-Non Finnish (NFE)

AF:

0.0736

AC:

80136

AN:

1088502

Other (OTH)

AF:

0.0673

AC:

3981

AN:

59180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4533

9065

13598

18130

22663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2980

5960

8940

11920

14900

<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:

0.0530

AC:

8070

AN:

152280

Hom.:

292

Cov.:

AF XY:

0.0539

AC XY:

4011

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.0155

AC:

643

AN:

41584

American (AMR)

AF:

0.0484

AC:

740

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0372

AC:

129

AN:

3472

East Asian (EAS)

AF:

0.0585

AC:

303

AN:

5176

South Asian (SAS)

AF:

0.0768

AC:

371

AN:

4828

European-Finnish (FIN)

AF:

0.0954

AC:

1011

AN:

10598

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0694

AC:

4722

AN:

68020

Other (OTH)

AF:

0.0545

AC:

115

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

390

780

1170

1560

1950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0541

Hom.:

120

Bravo

AF:

0.0476

Asia WGS

AF:

0.0880

AC:

307

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Achromatopsia 3

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.038

(source)

DANN

Benign

0.24

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over