Genetic Variant CNGA1:c.*352C>A (chr4-47936069-G-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001379270.1(CNGA1):c.*352C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000751 in 133,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

CNGA1
NM_001379270.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.626

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

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.*352C>A	3_prime_UTR	Exon 11 of 11	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.*352C>A	3_prime_UTR	Exon 11 of 11	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.*352C>A	3_prime_UTR	Exon 10 of 10	NP_001136036.2	P29973

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGA1	ENST00000514170.7	TSL:5 MANE Select	c.*352C>A	3_prime_UTR	Exon 11 of 11	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.*352C>A	3_prime_UTR	Exon 10 of 10	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.*352C>A	3_prime_UTR	Exon 11 of 11	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000751

AC:

AN:

133070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69952

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

4010

American (AMR)

AF:

0.00

AC:

AN:

5284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3824

East Asian (EAS)

AF:

0.00

AC:

AN:

6868

South Asian (SAS)

AF:

0.00

AC:

AN:

16682

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

554

European-Non Finnish (NFE)

AF:

0.0000122

AC:

AN:

82210

Other (OTH)

AF:

0.00

AC:

AN:

7334

⚠️ 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: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.22

(source)

DANN

Benign

0.34

PhyloP100

-0.63

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over