dbSNP rs921230822: CNGA1:c.*352C>T (chr4-47936069-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001379270.1(CNGA1):c.*352C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000351 in 285,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

CNGA1
NM_001379270.1 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

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>T	3_prime_UTR	Exon 11 of 11	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.*352C>T	3_prime_UTR	Exon 11 of 11	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.*352C>T	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>T	3_prime_UTR	Exon 11 of 11	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.*352C>T	3_prime_UTR	Exon 10 of 10	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.*352C>T	3_prime_UTR	Exon 11 of 11	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000225

AC:

AN:

133070

Hom.:

Cov.:

AF XY:

0.0000429

AC XY:

AN XY:

69952

show subpopulations

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:

0.0000599

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:

0.000136

AC:

AN:

7334

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151982

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41360

American (AMR)

AF:

0.000328

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10554

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.546

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:

0.00

Hom.:

Bravo

AF:

0.0000756

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.58

(source)

DANN

Benign

0.38

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over