ENST00000517327.5:c.*14+598C>T

Variant names:

• chr8-86568716-G-A
• rs4961199
• ENST00000517327.5:c.*14+598C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000517327.5(CNGB3):​c.*14+598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,154 control chromosomes in the GnomAD database, including 2,854 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 0.17 (2854 hom., cov: 32)
• Consequence: CNGB3 ENST00000517327.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01
• Publications: 12 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.21).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000517327.5	c.*14+598C>T		intron_variant	Intron 3 of 3	3		ENSP00000428329.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25479 AN: 152036 Hom.: 2836 Cov.: 32

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.168 AC: 25521 AN: 152154 Hom.: 2854 Cov.: 32 AF XY: 0.174 AC XY: 12942 AN XY: 74372

African (AFR) AF: 0.0881 AC: 3656 AN: 41518

American (AMR) AF: 0.366 AC: 5594 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 427 AN: 3470

East Asian (EAS) AF: 0.343 AC: 1772 AN: 5164

South Asian (SAS) AF: 0.202 AC: 974 AN: 4814

European-Finnish (FIN) AF: 0.162 AC: 1721 AN: 10594

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10888 AN: 67996

Other (OTH) AF: 0.167 AC: 353 AN: 2116

Alfa AF: 0.165 Hom.: 1211

Bravo AF: 0.185

Asia WGS AF: 0.275 AC: 956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	9.4
DANN	Benign	0.81
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4961199; hg19: chr8-87580944;