rs437920

chr16-57903991-G-Achr16-57903991-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001297.5(CNGB1):c.2635-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,611,120 control chromosomes in the GnomAD database, including 560,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46809 hom., cov: 32)
  • Exomes 𝑓: 0.84 (514088 hom.)
• Consequence: CNGB1 NM_001297.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00001391
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.181

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-57903991-G-A is Benign according to our data. Variant chr16-57903991-G-A is described in ClinVar as [Benign]. Clinvar id is 166895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57903991-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB1	NM_001297.5	c.2635-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000251102.13
CNGB1	NM_001286130.2	c.2617-10C>T		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB1	ENST00000251102.13	c.2635-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001297.5	P4
CNGB1	ENST00000564448.5	c.2617-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1		A2
CNGB1	ENST00000569643.1	n.292-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118400 AN: 151902 Hom.: 46783 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.802

GnomAD3 exomes AF: 0.812 AC: 200545 AN: 246984 Hom.: 82116 AF XY: 0.822 AC XY: 110075 AN XY: 133974

Gnomad AFR exome AF: 0.661

Gnomad AMR exome AF: 0.763

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.657

Gnomad SAS exome AF: 0.874

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.838 AC: 1222308 AN: 1459100 Hom.: 514088 Cov.: 43 AF XY: 0.840 AC XY: 609496 AN XY: 725852

Gnomad4 AFR exome AF: 0.655

Gnomad4 AMR exome AF: 0.765

Gnomad4 ASJ exome AF: 0.783

Gnomad4 EAS exome AF: 0.644

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.842

Gnomad4 NFE exome AF: 0.853

Gnomad4 OTH exome AF: 0.817

GnomAD4 genome AF: 0.779 AC: 118477 AN: 152020 Hom.: 46809 Cov.: 32 AF XY: 0.779 AC XY: 57851 AN XY: 74302

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.878

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.848

Gnomad4 OTH AF: 0.802

Alfa AF: 0.806 Hom.: 19244

Bravo AF: 0.768

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 27, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Retinitis pigmentosa 45 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.88
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs437920; hg19: chr16-57937895; COSMIC: COSV51901195; COSMIC: COSV51901195;