rs3758063

chr8-86673320-T-Cchr8-86673320-T-G

Variant summary

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

The NM_019098.5(CNGB3):c.339-2222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,218 control chromosomes in the GnomAD database, including 3,548 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 (3548 hom., cov: 32)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB3	NM_019098.5	c.339-2222A>G		intron_variant		ENST00000320005.6
CNGB3	XM_011517138.3	c.-76-2222A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB3	ENST00000320005.6	c.339-2222A>G		intron_variant		1	NM_019098.5	P1
CNGB3	ENST00000681746.1	c.339-2222A>G		intron_variant, NMD_transcript_variant
CNGB3	ENST00000680314.1	n.100-2222A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29356 AN: 152100 Hom.: 3550 Cov.: 32

Gnomad AFR AF: 0.0598

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.193 AC: 29350 AN: 152218 Hom.: 3548 Cov.: 32 AF XY: 0.199 AC XY: 14813 AN XY: 74428

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.185

Alfa AF: 0.204 Hom.: 1705

Bravo AF: 0.188

Asia WGS AF: 0.370 AC: 1286 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.8
Dann	Benign	0.78

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: rs3758063; hg19: chr8-87685548;