Genetic Variant CNGA1:c.545+26_545+28delTTT (chr4-47942012-CAAA-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001379270.1(CNGA1):c.545+26_545+28delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,159,706 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0043 ( 0 hom. )

Consequence

CNGA1
NM_001379270.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04

Publications

3 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:

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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_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.545+26_545+28delTTT	intron	N/A	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.545+26_545+28delTTT	intron	N/A	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.545+26_545+28delTTT	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.545+26_545+28delTTT	intron	N/A	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.545+26_545+28delTTT	intron	N/A	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.545+26_545+28delTTT	intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

127588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000294

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000705

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000151

Gnomad OTH

AF:

0.000588

GnomAD2 exomes

AF:

0.00585

AC:

812

AN:

138906

AF XY:

0.00604

show subpopulations

Gnomad AFR exome

AF:

0.00505

Gnomad AMR exome

AF:

0.00577

Gnomad ASJ exome

AF:

0.00138

Gnomad EAS exome

AF:

0.00475

Gnomad FIN exome

AF:

0.00763

Gnomad NFE exome

AF:

0.00688

Gnomad OTH exome

AF:

0.00395

GnomAD4 exome

AF:

0.00433

AC:

4473

AN:

1032116

Hom.:

AF XY:

0.00408

AC XY:

2143

AN XY:

525650

show subpopulations

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

African (AFR)

AF:

0.00443

AC:

100

AN:

22550

American (AMR)

AF:

0.00589

AC:

198

AN:

33604

Ashkenazi Jewish (ASJ)

AF:

0.00166

AC:

AN:

21636

East Asian (EAS)

AF:

0.00216

AC:

AN:

33274

South Asian (SAS)

AF:

0.00267

AC:

180

AN:

67414

European-Finnish (FIN)

AF:

0.00393

AC:

150

AN:

38178

Middle Eastern (MID)

AF:

0.00285

AC:

AN:

3856

European-Non Finnish (NFE)

AF:

0.00463

AC:

3548

AN:

766648

Other (OTH)

AF:

0.00396

AC:

178

AN:

44956

⚠️ 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: 0.274

Heterozygous variant carriers

412

824

1237

1649

2061

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

162

324

486

648

810

<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:

0.000125

AC:

AN:

127590

Hom.:

Cov.:

AF XY:

0.0000490

AC XY:

AN XY:

61232

show subpopulations

African (AFR)

AF:

0.0000294

AC:

AN:

34054

American (AMR)

AF:

0.00

AC:

AN:

12686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3058

East Asian (EAS)

AF:

0.00

AC:

AN:

4446

South Asian (SAS)

AF:

0.00

AC:

AN:

3960

European-Finnish (FIN)

AF:

0.000705

AC:

AN:

7092

Middle Eastern (MID)

AF:

0.00

AC:

AN:

242

European-Non Finnish (NFE)

AF:

0.000151

AC:

AN:

59550

Other (OTH)

AF:

0.000585

AC:

AN:

1710

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

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:

0.00127

Hom.:

1208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

4-47942012-CAAAAAA-CAAA

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