rs2033249

Variant names:

• chr16-57887652-G-A
• rs2033249
• NM_001297.5:c.3462+203C>T

Variant summary

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

The NM_001297.5(CNGB1):​c.3462+203C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,912 control chromosomes in the GnomAD database, including 11,987 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 0.38 (11987 hom., cov: 32)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 4 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 (NFE) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	NM_001297.5	MANE Select	c.3462+203C>T		intron	N/A	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.3444+203C>T		intron	N/A	NP_001273059.1	Q14028-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	ENST00000251102.13	TSL:1 MANE Select	c.3462+203C>T		intron	N/A	ENSP00000251102.8	Q14028-1
	CNGB1	ENST00000564448.5	TSL:1	c.3444+203C>T		intron	N/A	ENSP00000454633.1	Q14028-4
	CNGB1	ENST00000565942.1	TSL:5	c.288-3195C>T		intron	N/A	ENSP00000455964.1	H3BQW3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57896 AN: 151794 Hom.: 11984 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.381 AC: 57916 AN: 151912 Hom.: 11987 Cov.: 32 AF XY: 0.379 AC XY: 28104 AN XY: 74224

African (AFR) AF: 0.225 AC: 9331 AN: 41410

American (AMR) AF: 0.355 AC: 5420 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1984 AN: 3468

East Asian (EAS) AF: 0.297 AC: 1532 AN: 5154

South Asian (SAS) AF: 0.413 AC: 1987 AN: 4814

European-Finnish (FIN) AF: 0.431 AC: 4540 AN: 10524

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.467 AC: 31732 AN: 67958

Other (OTH) AF: 0.391 AC: 825 AN: 2108

Alfa AF: 0.417 Hom.: 3473

Bravo AF: 0.365

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.032
DANN	Benign	0.85
PhyloP100		-0.43
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: rs2033249; hg19: chr16-57921556;