8-86574166-C-T

Variant names:

• chr8-86574166-C-T
• rs28471019
• ENST00000517327.5:c.276+4523G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000517327.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	NM_019098.5	MANE Select	c.*1638G>A		downstream_gene	N/A	NP_061971.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	ENST00000517327.5	TSL:3	c.276+4523G>A		intron	N/A	ENSP00000428329.1	H0YAZ4
	CNGB3	ENST00000681746.1		n.*2479G>A		non_coding_transcript_exon	Exon 19 of 19	ENSP00000505959.1	A0A5J6DSN8
	CNGB3	ENST00000681746.1		n.*2479G>A		3_prime_UTR	Exon 19 of 19	ENSP00000505959.1	A0A5J6DSN8

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.134 AC: 5533 AN: 41412

American (AMR) AF: 0.0691 AC: 1055 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3470

East Asian (EAS) AF: 0.100 AC: 518 AN: 5180

South Asian (SAS) AF: 0.0762 AC: 367 AN: 4818

European-Finnish (FIN) AF: 0.107 AC: 1127 AN: 10534

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0872 AC: 5926 AN: 67942

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0985 Hom.: 217

Bravo AF: 0.0977

Asia WGS AF: 0.120 AC: 415 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Achromatopsia 3 (1)
-	-	1	not provided (1)
-	-	1	Severe early-childhood-onset retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.4
DANN	Benign	0.38
PhyloP100		-0.50
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: rs28471019; hg19: chr8-87586394;