16-57924255-C-T

Variant names:

• chr16-57924255-C-T
• rs3784901
• NM_001297.5:c.1536-875G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297.5(CNGB1):​c.1536-875G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 151,888 control chromosomes in the GnomAD database, including 2,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2334 hom., cov: 31)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• CNGB1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 45

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.1536-875G>A		intron_variant	Intron 17 of 32	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.1518-875G>A		intron_variant	Intron 17 of 32		NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.1536-875G>A		intron_variant	Intron 17 of 32	1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5	c.1518-875G>A		intron_variant	Intron 17 of 32	1		ENSP00000454633.1
CNGB1	ENST00000564450.1	n.121-875G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25038 AN: 151770 Hom.: 2330 Cov.: 31

Gnomad AFR AF: 0.0870

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.174

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.165 AC: 25056 AN: 151888 Hom.: 2334 Cov.: 31 AF XY: 0.169 AC XY: 12540 AN XY: 74198

African (AFR) AF: 0.0868 AC: 3598 AN: 41428

American (AMR) AF: 0.171 AC: 2619 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3466

East Asian (EAS) AF: 0.167 AC: 863 AN: 5166

South Asian (SAS) AF: 0.279 AC: 1330 AN: 4770

European-Finnish (FIN) AF: 0.229 AC: 2417 AN: 10540

Middle Eastern (MID) AF: 0.307 AC: 89 AN: 290

European-Non Finnish (NFE) AF: 0.189 AC: 12819 AN: 67940

Other (OTH) AF: 0.178 AC: 375 AN: 2106

Alfa AF: 0.173 Hom.: 1823

Bravo AF: 0.157

Asia WGS AF: 0.236 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.28
DANN	Benign	0.30
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3784901; hg19: chr16-57958159;