Variant NM_001379270.1:c.288-26G>C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001379270.1(CNGA1):c.288-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,326,930 control chromosomes in the GnomAD database, including 435,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.83 ( 52558 hom., cov: 29)

Exomes 𝑓: 0.81 ( 382899 hom. )

Consequence

CNGA1
NM_001379270.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.157

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 4-47943438-C-G is Benign according to our data. Variant chr4-47943438-C-G is described in ClinVar as [Benign]. Clinvar id is 1278730.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGA1	NM_001379270.1 link	c.288-26G>C		intron_variant	Intron 6 of 10	ENST00000514170.7	NP_001366199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGA1	ENST00000514170.7 link	c.288-26G>C		intron_variant	Intron 6 of 10	5	NM_001379270.1	ENSP00000426862.3		P29973

Frequencies

GnomAD3 genomes

AF:

0.831

AC:

126001

AN:

151670

Hom.:

52516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.851

Gnomad AMI

AF:

0.829

Gnomad AMR

AF:

0.863

Gnomad ASJ

AF:

0.695

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.794

Gnomad FIN

AF:

0.881

Gnomad MID

AF:

0.755

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.808

GnomAD3 exomes

AF:

0.826

AC:

95715

AN:

115822

Hom.:

39834

AF XY:

0.820

AC XY:

50852

AN XY:

62008

show subpopulations

Gnomad AFR exome

AF:

0.848

Gnomad AMR exome

AF:

0.890

Gnomad ASJ exome

AF:

0.686

Gnomad EAS exome

AF:

0.974

Gnomad SAS exome

AF:

0.788

Gnomad FIN exome

AF:

0.875

Gnomad NFE exome

AF:

0.797

Gnomad OTH exome

AF:

0.803

GnomAD4 exome

AF:

0.806

AC:

947050

AN:

1175142

Hom.:

382899

Cov.:

AF XY:

0.805

AC XY:

472782

AN XY:

587542

show subpopulations

Gnomad4 AFR exome

AF:

0.848

Gnomad4 AMR exome

AF:

0.883

Gnomad4 ASJ exome

AF:

0.685

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.788

Gnomad4 FIN exome

AF:

0.875

Gnomad4 NFE exome

AF:

0.798

Gnomad4 OTH exome

AF:

0.804

GnomAD4 genome

AF:

0.831

AC:

126102

AN:

151788

Hom.:

52558

Cov.:

AF XY:

0.833

AC XY:

61784

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.851

Gnomad4 AMR

AF:

0.863

Gnomad4 ASJ

AF:

0.695

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.793

Gnomad4 FIN

AF:

0.881

Gnomad4 NFE

AF:

0.803

Gnomad4 OTH

AF:

0.811

Alfa

AF:

0.793

Hom.:

8486

Bravo

AF:

0.831

Asia WGS

AF:

0.887

AC:

3083

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

8.5

DANN

Benign

0.55

BranchPoint Hunter

3.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over