rs199591689

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001297.5(CNGB1):c.159+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00432 in 1,613,968 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 23 hom. )

Consequence

CNGB1
NM_001297.5 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -0.130

Variant links:

Genes affected

CNGB1 (HGNC:2151): (cyclic nucleotide gated channel subunit beta 1) In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

CNGB1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-57967114-G-A is Benign according to our data. Variant chr16-57967114-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257959.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=2, Uncertain_significance=1}. Variant chr16-57967114-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00271 (412/152216) while in subpopulation NFE AF= 0.00481 (327/67988). AF 95% confidence interval is 0.00438. There are 0 homozygotes in gnomad4. There are 190 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5 link	c.159+14C>T	intron_variant	Intron 2 of 32	ENST00000251102.13	NP_001288.3	Q14028-1
CNGB1	NM_001286130.2 link	c.159+14C>T	intron_variant	Intron 2 of 32		NP_001273059.1	Q14028-4
CNGB1	NM_001135639.2 link	c.159+14C>T	intron_variant	Intron 2 of 12		NP_001129111.1	Q14028-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13 link	c.159+14C>T		intron_variant	Intron 2 of 32	1	NM_001297.5	ENSP00000251102.8		Q14028-1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000869

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00481

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00239

AC:

596

AN:

249452

Hom.:

AF XY:

0.00228

AC XY:

309

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.00116

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.000111

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00399

Gnomad OTH exome

AF:

0.00314

GnomAD4 exome

AF:

0.00449

AC:

6557

AN:

1461752

Hom.:

Cov.:

AF XY:

0.00441

AC XY:

3205

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000337

Gnomad4 NFE exome

AF:

0.00554

Gnomad4 OTH exome

AF:

0.00348

GnomAD4 genome

AF:

0.00271

AC:

412

AN:

152216

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

190

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00481

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000973

Hom.:

Bravo

AF:

0.00294

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Uncertain:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis pigmentosa 45

Benign:1

Oct 09, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

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

-0.82

CADD

Benign

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.20

Position offset: 7

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