16-57903952-G-T

Position:

• chr16-57903952-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001297.5(CNGB1):​c.2664C>A​(p.Ala888Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,682 control chromosomes in the GnomAD database, including 11,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A888A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.15 (1967 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9437 hom.)
• Consequence: CNGB1 NM_001297.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -8.35

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-57903952-G-T is Benign according to our data. Variant chr16-57903952-G-T is described in ClinVar as [Benign]. Clinvar id is 93700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-57903952-G-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-8.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.2664C>A	p.Ala888Ala	synonymous_variant	27/33	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.2646C>A	p.Ala882Ala	synonymous_variant	27/33		NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.2664C>A	p.Ala888Ala	synonymous_variant	27/33	1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5	c.2646C>A	p.Ala882Ala	synonymous_variant	27/33	1		ENSP00000454633.1
CNGB1	ENST00000569643.1	n.321C>A		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22158 AN: 152064 Hom.: 1964 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.117 AC: 29178 AN: 248746 Hom.: 2075 AF XY: 0.113 AC XY: 15290 AN XY: 134984

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.0909

Gnomad EAS exome AF: 0.0818

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0523

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.108 AC: 158551 AN: 1461500 Hom.: 9437 Cov.: 55 AF XY: 0.108 AC XY: 78517 AN XY: 727052

Gnomad4 AFR exome AF: 0.261

Gnomad4 AMR exome AF: 0.160

Gnomad4 ASJ exome AF: 0.0937

Gnomad4 EAS exome AF: 0.0642

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0536

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.146 AC: 22200 AN: 152182 Hom.: 1967 Cov.: 33 AF XY: 0.142 AC XY: 10591 AN XY: 74390

Gnomad4 AFR AF: 0.254

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0940

Gnomad4 EAS AF: 0.0819

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0484

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.134

Alfa AF: 0.105 Hom.: 3683

EpiCase AF: 0.100

EpiControl AF: 0.101

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Oct 23, 2013

- -

Retinal dystrophy Benign:1

Benign, no assertion criteria provided

clinical testing

Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg

Jan 01, 2013

- -

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	-0.88
CADD	Benign	0.030
DANN	Benign	0.31

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

Other links and lift over

dbSNP: rs413562; hg19: chr16-57937856;