Genetic Variant NM_001379270.1:c.225-33C>T (chr4-47949928-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_001379270.1(CNGA1):c.225-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,604,472 control chromosomes in the GnomAD database, including 536,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55480 hom., cov: 33)

Exomes 𝑓: 0.81 ( 481233 hom. )

Consequence

CNGA1
NM_001379270.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.142

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

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-47949928-G-A is Benign according to our data. Variant chr4-47949928-G-A is described in ClinVar as [Benign]. Clinvar id is 1217359.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.225-33C>T		intron_variant	Intron 5 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.225-33C>T		intron_variant	Intron 5 of 10	5	NM_001379270.1	ENSP00000426862.3		P29973

Frequencies

GnomAD3 genomes

AF:

0.851

AC:

129435

AN:

152128

Hom.:

55422

Cov.:

show subpopulations

Gnomad AFR

AF:

0.920

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.871

Gnomad ASJ

AF:

0.694

Gnomad EAS

AF:

0.979

Gnomad SAS

AF:

0.794

Gnomad FIN

AF:

0.880

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.826

GnomAD3 exomes

AF:

0.837

AC:

207969

AN:

248476

Hom.:

87742

AF XY:

0.827

AC XY:

111452

AN XY:

134788

show subpopulations

Gnomad AFR exome

AF:

0.925

Gnomad AMR exome

AF:

0.909

Gnomad ASJ exome

AF:

0.687

Gnomad EAS exome

AF:

0.974

Gnomad SAS exome

AF:

0.791

Gnomad FIN exome

AF:

0.873

Gnomad NFE exome

AF:

0.801

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.813

AC:

1180078

AN:

1452226

Hom.:

481233

Cov.:

AF XY:

0.810

AC XY:

586017

AN XY:

723136

show subpopulations

Gnomad4 AFR exome

AF:

0.924

Gnomad4 AMR exome

AF:

0.902

Gnomad4 ASJ exome

AF:

0.688

Gnomad4 EAS exome

AF:

0.973

Gnomad4 SAS exome

AF:

0.790

Gnomad4 FIN exome

AF:

0.874

Gnomad4 NFE exome

AF:

0.802

Gnomad4 OTH exome

AF:

0.812

GnomAD4 genome

AF:

0.851

AC:

129554

AN:

152246

Hom.:

55480

Cov.:

AF XY:

0.852

AC XY:

63439

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.921

Gnomad4 AMR

AF:

0.871

Gnomad4 ASJ

AF:

0.694

Gnomad4 EAS

AF:

0.979

Gnomad4 SAS

AF:

0.793

Gnomad4 FIN

AF:

0.880

Gnomad4 NFE

AF:

0.803

Gnomad4 OTH

AF:

0.829

Alfa

AF:

0.818

Hom.:

12773

Bravo

AF:

0.854

Asia WGS

AF:

0.893

AC:

3106

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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

- -

Retinitis pigmentosa 49

Benign:1

Jul 22, 2021

Genome-Nilou Lab

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

-0.89

CADD

Benign

1.7

DANN

Benign

0.22

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