rs58990587

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001298.3(CNGA3):c.215+46T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,542,812 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 17 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 18 hom. )

Consequence

CNGA3
NM_001298.3 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.969

Publications

4 publications found

Variant links:

Genes affected

CNGA3 (HGNC:2150): (cyclic nucleotide gated channel subunit alpha 3) This gene encodes a member of the cyclic nucleotide-gated cation channel protein family which is required for normal vision and olfactory signal transduction. Mutations in this gene are associated with achromatopsia (rod monochromacy) and color blindness. Two alternatively spliced transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

CNGA3 Gene-Disease associations (from GenCC):

achromatopsia 2
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia
CNGA3-related retinopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
achromatopsia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CNGA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 2-98377846-T-A is Benign according to our data. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-98377846-T-A is described in CliVar as Likely_benign. Clinvar id is 1254794.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00901 (1372/152212) while in subpopulation AFR AF = 0.0307 (1273/41524). AF 95% confidence interval is 0.0293. There are 17 homozygotes in GnomAd4. There are 625 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGA3	NM_001298.3 link	c.215+46T>A		intron_variant	Intron 3 of 7	ENST00000272602.7	NP_001289.1	Q16281-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CNGA3	ENST00000272602.7 link	c.215+46T>A	intron_variant	Intron 3 of 7	1	NM_001298.3	ENSP00000272602.2	Q16281-1
CNGA3	ENST00000436404.6 link	c.215+46T>A	intron_variant	Intron 3 of 6	1		ENSP00000410070.2	Q16281-2
CNGA3	ENST00000409937.1 link	n.203+46T>A	intron_variant	Intron 2 of 7	2

Frequencies

GnomAD3 genomes

AF:

0.00895

AC:

1361

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0305

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00524

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:

0.0000294

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00230

AC:

427

AN:

185940

AF XY:

0.00182

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000505

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000900

AC:

1252

AN:

1390600

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

552

AN XY:

689330

show subpopulations

African (AFR)

AF:

0.0319

AC:

1019

AN:

31956

American (AMR)

AF:

0.00185

AC:

AN:

38984

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24534

East Asian (EAS)

AF:

0.00

AC:

AN:

38260

South Asian (SAS)

AF:

0.000150

AC:

AN:

80142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50712

Middle Eastern (MID)

AF:

0.000713

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1064152

Other (OTH)

AF:

0.00213

AC:

123

AN:

57652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

134

200

267

334

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00901

AC:

1372

AN:

152212

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

625

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0307

AC:

1273

AN:

41524

American (AMR)

AF:

0.00523

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

134

201

268

335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.000132

Hom.:

107

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 17, 2021

GeneDx

Significance:Likely 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

-0.83

CADD

Benign

7.2

(source)

DANN

Benign

0.26

PhyloP100

0.97

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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