rs3784900

Positions:

• chr16-57921912-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297.5(CNGB1):​c.1643+1361T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,200 control chromosomes in the GnomAD database, including 2,048 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 0.15 (2048 hom., cov: 31)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.1643+1361T>C		intron_variant		ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.1625+1361T>C		intron_variant			NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.1643+1361T>C		intron_variant		1	NM_001297.5	ENSP00000251102	P4
CNGB1	ENST00000564448.5	c.1625+1361T>C		intron_variant		1		ENSP00000454633	A2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23494 AN: 152082 Hom.: 2047 Cov.: 31

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.154 AC: 23500 AN: 152200 Hom.: 2048 Cov.: 31 AF XY: 0.157 AC XY: 11673 AN XY: 74408

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.0885

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.167

Alfa AF: 0.183 Hom.: 2717

Bravo AF: 0.145

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.82

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: rs3784900; hg19: chr16-57955816;