rs3758063

Variant names:

• chr8-86673320-T-C
• rs3758063
• NM_019098.5:c.339-2222A>G

Your query was ambiguous. Multiple possible variants found:

• chr8-86673320-T-C
• chr8-86673320-T-G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CNGB3 Gene-Disease associations (from GenCC):

• achromatopsia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• CNGB3-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.339-2222A>G		intron_variant	Intron 3 of 17	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.-76-2222A>G		intron_variant	Intron 1 of 15		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.339-2222A>G		intron_variant	Intron 3 of 17	1	NM_019098.5	ENSP00000316605.5
CNGB3	ENST00000680314.1	n.100-2222A>G		intron_variant	Intron 1 of 2
CNGB3	ENST00000681746.1	n.339-2222A>G		intron_variant	Intron 3 of 18			ENSP00000505959.1

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

African (AFR) AF: 0.0597 AC: 2481 AN: 41558

American (AMR) AF: 0.257 AC: 3926 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2173 AN: 5176

South Asian (SAS) AF: 0.365 AC: 1763 AN: 4826

European-Finnish (FIN) AF: 0.242 AC: 2558 AN: 10586

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15194 AN: 67998

Other (OTH) AF: 0.185 AC: 390 AN: 2112

Alfa AF: 0.205 Hom.: 1913

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
PhyloP100		-0.063
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: rs3758063; hg19: chr8-87685548;