NM_019098.5:c.338+3287T>C

Variant names:

• chr8-86723244-A-G
• rs1561688
• NM_019098.5:c.338+3287T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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)

ENSG00000253778 (HGNC:58258):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.338+3287T>C		intron_variant	Intron 3 of 17	ENST00000320005.6	NP_061971.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.338+3287T>C		intron_variant	Intron 3 of 17	1	NM_019098.5	ENSP00000316605.5

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

African (AFR) AF: 0.0617 AC: 2564 AN: 41546

American (AMR) AF: 0.206 AC: 3131 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1047 AN: 3470

East Asian (EAS) AF: 0.0941 AC: 486 AN: 5164

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4820

European-Finnish (FIN) AF: 0.250 AC: 2641 AN: 10564

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.248 AC: 16822 AN: 67962

Other (OTH) AF: 0.199 AC: 421 AN: 2114

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
PhyloP100		0.32
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: rs1561688; hg19: chr8-87735472;