Genetic Variant CNGA1:c.545+26_545+28dupTTT (chr4-47942012-C-CAAA) – 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+28dupTTT 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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00047 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CNGA1
NM_001379270.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.500

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+28dupTTT	intron	N/A	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.545+26_545+28dupTTT	intron	N/A	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.545+26_545+28dupTTT	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+28_545+29insTTT	intron	N/A	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.545+28_545+29insTTT	intron	N/A	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.545+28_545+29insTTT	intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

127604

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00104

AC:

144

AN:

138906

AF XY:

0.00111

show subpopulations

Gnomad AFR exome

AF:

0.000235

Gnomad AMR exome

AF:

0.000817

Gnomad ASJ exome

AF:

0.00292

Gnomad EAS exome

AF:

0.000396

Gnomad FIN exome

AF:

0.000553

Gnomad NFE exome

AF:

0.000986

Gnomad OTH exome

AF:

0.00113

GnomAD4 exome

AF:

0.000470

AC:

488

AN:

1037244

Hom.:

Cov.:

AF XY:

0.000506

AC XY:

267

AN XY:

528090

show subpopulations

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

African (AFR)

AF:

0.000397

AC:

AN:

22670

American (AMR)

AF:

0.000474

AC:

AN:

33758

Ashkenazi Jewish (ASJ)

AF:

0.00111

AC:

AN:

21698

East Asian (EAS)

AF:

0.0000597

AC:

AN:

33480

South Asian (SAS)

AF:

0.000992

AC:

AN:

67570

European-Finnish (FIN)

AF:

0.000208

AC:

AN:

38436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3864

European-Non Finnish (NFE)

AF:

0.000454

AC:

350

AN:

770570

Other (OTH)

AF:

0.000265

AC:

AN:

45198

⚠️ 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: 0.276

Heterozygous variant carriers

145

193

241

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

127604

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

61216

African (AFR)

AF:

0.00

AC:

AN:

34002

American (AMR)

AF:

0.00

AC:

AN:

12672

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3058

East Asian (EAS)

AF:

0.00

AC:

AN:

4462

South Asian (SAS)

AF:

0.00

AC:

AN:

3984

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7096

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59570

Other (OTH)

AF:

0.00

AC:

AN:

1702

Alfa

AF:

0.000637

Hom.:

1208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.50

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-47942012-CAAAAAA-CAAAAAAAAA

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