8-86574165-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000517327.5(CNGB3):c.276+4524C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,954 control chromosomes in the GnomAD database, including 28,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.59 (28316 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CNGB3 ENST00000517327.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.647

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-86574165-G-T is Benign according to our data. Variant chr8-86574165-G-T is described in ClinVar as [Benign]. Clinvar id is 363844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB3	NM_019098.5			downstream_gene_variant		ENST00000320005.6
CNGB3	XM_011517138.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB3	ENST00000517327.5	c.276+4524C>A		intron_variant		3
CNGB3	ENST00000681746.1	c.*2480C>A		3_prime_UTR_variant, NMD_transcript_variant	19/19
CNGB3	ENST00000320005.6			downstream_gene_variant		1	NM_019098.5	P1
CNGB3	ENST00000681546.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89720 AN: 151834 Hom.: 28308 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.712

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.636

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.580

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AC XY: 0 AN XY: 0

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.591 AC: 89744 AN: 151952 Hom.: 28316 Cov.: 31 AF XY: 0.591 AC XY: 43874 AN XY: 74242

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.680

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.637

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.572

Alfa AF: 0.665 Hom.: 25195

Bravo AF: 0.579

Asia WGS AF: 0.503 AC: 1748 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Severe early-childhood-onset retinal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Achromatopsia 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.27
Dann	Benign	0.47

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: rs990192; hg19: chr8-87586393;