Genetic Variant CNGA1:c.545+27_545+28dupTT (chr4-47942012-C-CAA) – 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+27_545+28dupTT 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 0.00021 ( 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: -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+27_545+28dupTT	intron	N/A	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.545+27_545+28dupTT	intron	N/A	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.545+27_545+28dupTT	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+29insTT	intron	N/A	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.545+28_545+29insTT	intron	N/A	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.545+28_545+29insTT	intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.000212

AC:

AN:

127588

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000789

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000141

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00649

AC:

902

AN:

138906

AF XY:

0.00696

show subpopulations

Gnomad AFR exome

AF:

0.00458

Gnomad AMR exome

AF:

0.00255

Gnomad ASJ exome

AF:

0.0141

Gnomad EAS exome

AF:

0.00139

Gnomad FIN exome

AF:

0.00365

Gnomad NFE exome

AF:

0.00706

Gnomad OTH exome

AF:

0.00677

GnomAD4 exome

AF:

0.00426

AC:

4396

AN:

1032466

Hom.:

Cov.:

AF XY:

0.00426

AC XY:

2240

AN XY:

525620

show subpopulations

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

African (AFR)

AF:

0.00496

AC:

112

AN:

22580

American (AMR)

AF:

0.00247

AC:

AN:

33654

Ashkenazi Jewish (ASJ)

AF:

0.00758

AC:

163

AN:

21516

East Asian (EAS)

AF:

0.000479

AC:

AN:

33390

South Asian (SAS)

AF:

0.00651

AC:

436

AN:

66950

European-Finnish (FIN)

AF:

0.00240

AC:

AN:

38290

Middle Eastern (MID)

AF:

0.00416

AC:

AN:

3846

European-Non Finnish (NFE)

AF:

0.00430

AC:

3298

AN:

767274

Other (OTH)

AF:

0.00400

AC:

180

AN:

44966

⚠️ 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: 0.283

Heterozygous variant carriers

380

759

1139

1518

1898

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

240

360

480

600

<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:

0.000212

AC:

AN:

127588

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

61214

show subpopulations

African (AFR)

AF:

0.000324

AC:

AN:

33996

American (AMR)

AF:

0.0000789

AC:

AN:

12670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3056

East Asian (EAS)

AF:

0.00

AC:

AN:

4462

South Asian (SAS)

AF:

0.00

AC:

AN:

3984

European-Finnish (FIN)

AF:

0.000141

AC:

AN:

7094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

266

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

59566

Other (OTH)

AF:

0.00

AC:

AN:

1702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.00541

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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