rs6819506

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_001379270.1(CNGA1):c.288-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,326,930 control chromosomes in the GnomAD database, including 435,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.83 ( 52558 hom., cov: 29)

Exomes 𝑓: 0.81 ( 382899 hom. )

Consequence

CNGA1
NM_001379270.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.157

Publications

9 publications found

Variant links:

Genes affected

CNGA1 (HGNC:2148): (cyclic nucleotide gated channel subunit alpha 1) The protein encoded by this gene is involved in phototransduction. Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. This represents the last step in the phototransduction pathway. Defects in this gene are a cause of retinitis pigmentosa autosomal recessive (ARRP) disease. Multiple transcript variants have been found for this gene. [provided by RefSeq, Oct 2019]

CNGA1 links:

NIPAL1 (HGNC:27194): (NIPA like domain containing 1) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

NIPAL1 links:

LOC101927157 (HGNC:):

LOC101927157 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 4-47943438-C-G is Benign according to our data. Variant chr4-47943438-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379270.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGA1	NM_001379270.1	MANE Select	c.288-26G>C	intron	N/A	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.288-26G>C	intron	N/A	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.288-26G>C	intron	N/A	NP_001136036.2	P29973

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGA1	ENST00000514170.7	TSL:5 MANE Select	c.288-26G>C	intron	N/A	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.288-26G>C	intron	N/A	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.288-26G>C	intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126001

AN:

151670

Hom.:

52516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.851

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.794

Gnomad FIN

AF:

0.881

Gnomad MID

AF:

0.755

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.808

GnomAD2 exomes

AF:

0.826

AC:

95715

AN:

115822

AF XY:

0.820

show subpopulations

Gnomad AFR exome

AF:

0.848

Gnomad AMR exome

AF:

0.890

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.974

Gnomad FIN exome

AF:

0.875

Gnomad NFE exome

AF:

0.797

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.806

AC:

947050

AN:

1175142

Hom.:

382899

Cov.:

AF XY:

0.805

AC XY:

472782

AN XY:

587542

show subpopulations

African (AFR)

AF:

0.848

AC:

21310

AN:

25134

American (AMR)

AF:

0.883

AC:

19664

AN:

22260

Ashkenazi Jewish (ASJ)

AF:

0.685

AC:

15092

AN:

22030

East Asian (EAS)

AF:

0.972

AC:

33234

AN:

34178

South Asian (SAS)

AF:

0.788

AC:

52296

AN:

66396

European-Finnish (FIN)

AF:

0.875

AC:

41935

AN:

47926

Middle Eastern (MID)

AF:

0.695

AC:

2622

AN:

3770

European-Non Finnish (NFE)

AF:

0.798

AC:

720845

AN:

903622

Other (OTH)

AF:

0.804

AC:

40052

AN:

49826

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

8262

16524

24786

33048

41310

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16134

32268

48402

64536

80670

<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:

0.831

AC:

126102

AN:

151788

Hom.:

52558

Cov.:

AF XY:

0.833

AC XY:

61784

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.851

AC:

35208

AN:

41382

American (AMR)

AF:

0.863

AC:

13159

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.695

AC:

2410

AN:

3468

East Asian (EAS)

AF:

0.979

AC:

5070

AN:

5180

South Asian (SAS)

AF:

0.793

AC:

3806

AN:

4800

European-Finnish (FIN)

AF:

0.881

AC:

9222

AN:

10472

Middle Eastern (MID)

AF:

0.753

AC:

220

AN:

292

European-Non Finnish (NFE)

AF:

0.803

AC:

54551

AN:

67946

Other (OTH)

AF:

0.811

AC:

1702

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1058

2116

3173

4231

5289

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.793

Hom.:

8486

Bravo

AF:

0.831

Asia WGS

AF:

0.887

AC:

3083

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.5

(source)

DANN

Benign

0.55

PhyloP100

0.16

BranchPoint Hunter

3.0

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over