8-86573923-A-G

Position:

• chr8-86573923-A-G

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.277-4536T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 152,160 control chromosomes in the GnomAD database, including 62,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (62931 hom., cov: 32)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: CNGB3 ENST00000517327.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.239

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=-0.94).
• BP6: Variant 8-86573923-A-G is Benign according to our data. Variant chr8-86573923-A-G is described in ClinVar as [Benign]. Clinvar id is 369616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000517327.5	c.277-4536T>C		intron_variant		3		ENSP00000428329
CNGB3	ENST00000681746.1			downstream_gene_variant				ENSP00000505959

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137946 AN: 152040 Hom.: 62863 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.898

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.871

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.898

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.875

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

Gnomad4 FIN exome AF: 1.00

GnomAD4 genome AF: 0.907 AC: 138075 AN: 152158 Hom.: 62931 Cov.: 32 AF XY: 0.904 AC XY: 67254 AN XY: 74384

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.906

Gnomad4 ASJ AF: 0.871

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.898

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.874

Alfa AF: 0.896 Hom.: 59274

Bravo AF: 0.909

Asia WGS AF: 0.757 AC: 2634 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Stargardt Disease, Recessive Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Achromatopsia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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	-0.94
CADD	Benign	0.80
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs990193; hg19: chr8-87586151;