8-86574166-C-T

Position:

• chr8-86574166-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000517327.5(CNGB3):​c.276+4523G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 151,936 control chromosomes in the GnomAD database, including 832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (832 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CNGB3 ENST00000517327.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.497

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-86574166-C-T is Benign according to our data. Variant chr8-86574166-C-T is described in ClinVar as [Benign]. Clinvar id is 363845.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5			downstream_gene_variant		ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3			downstream_gene_variant			XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000517327.5	c.276+4523G>A		intron_variant		3		ENSP00000428329
CNGB3	ENST00000681746.1	c.*2479G>A		3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000505959
CNGB3	ENST00000320005.6			downstream_gene_variant		1	NM_019098.5	ENSP00000316605	P1
CNGB3	ENST00000681546.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 14973 AN: 151818 Hom.: 833 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0998

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0858

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0987 AC: 14990 AN: 151936 Hom.: 832 Cov.: 32 AF XY: 0.0990 AC XY: 7345 AN XY: 74212

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.100

Gnomad4 SAS AF: 0.0762

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0872

Gnomad4 OTH AF: 0.0863

Alfa AF: 0.105 Hom.: 118

Bravo AF: 0.0977

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Severe early-childhood-onset retinal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 12, 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. -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.38

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: rs28471019; hg19: chr8-87586394;