rs2033249

Positions:

• chr16-57887652-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.3462+203C>T		intron_variant		ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.3444+203C>T		intron_variant			NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.3462+203C>T		intron_variant		1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5	c.3444+203C>T		intron_variant		1		ENSP00000454633.1
CNGB1	ENST00000565942.1	c.288-3195C>T		intron_variant		5		ENSP00000455964.1

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

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.391

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.032
DANN	Benign	0.85

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: rs2033249; hg19: chr16-57921556;