rs1561688

Positions:

• chr8-86723244-A-G

Variant summary

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

The NM_019098.5(CNGB3):​c.338+3287T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,076 control chromosomes in the GnomAD database, including 3,352 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 0.19 (3352 hom., cov: 32)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

Genes affected

CNGB3 (HGNC:2153): (cyclic nucleotide gated channel subunit beta 3) This gene encodes the beta subunit of a cyclic nucleotide-gated ion channel. The encoded beta subunit appears to play a role in modulation of channel function in cone photoreceptors. This heterotetrameric channel is necessary for sensory transduction, and mutations in this gene have been associated with achromatopsia 3, progressive cone dystrophy, and juvenile macular degeneration, also known as Stargardt Disease. [provided by RefSeq, Feb 2010]

ENSG00000254115 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.291 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.338+3287T>C		intron_variant		ENST00000320005.6	NP_061971.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.338+3287T>C		intron_variant		1	NM_019098.5	ENSP00000316605.5
ENSG00000254115	ENST00000519041.1	n.448+15250A>G		intron_variant		3
CNGB3	ENST00000519777.1	n.320+3287T>C		intron_variant		2
CNGB3	ENST00000681746.1	n.338+3287T>C		intron_variant				ENSP00000505959.1

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28816 AN: 151958 Hom.: 3348 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.0937

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.194

Gnomad NFE AF: 0.248

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.190 AC: 28833 AN: 152076 Hom.: 3352 Cov.: 32 AF XY: 0.192 AC XY: 14245 AN XY: 74340

Gnomad4 AFR AF: 0.0617

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.302

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.304

Gnomad4 FIN AF: 0.250

Gnomad4 NFE AF: 0.248

Gnomad4 OTH AF: 0.199

Alfa AF: 0.211 Hom.: 451

Bravo AF: 0.179

Asia WGS AF: 0.227 AC: 792 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.61

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: rs1561688; hg19: chr8-87735472;