8-86574165-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.647
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 Protein UniProt
CNGB3NM_019098.5 linkuse as main transcript downstream_gene_variant ENST00000320005.6 NP_061971.3
CNGB3XM_011517138.3 linkuse as main transcript downstream_gene_variant XP_011515440.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNGB3ENST00000517327.5 linkuse as main transcriptc.276+4524C>A intron_variant 3 ENSP00000428329
CNGB3ENST00000681746.1 linkuse as main transcriptc.*2480C>A 3_prime_UTR_variant, NMD_transcript_variant 19/19 ENSP00000505959
CNGB3ENST00000320005.6 linkuse as main transcript downstream_gene_variant 1 NM_019098.5 ENSP00000316605 P1Q9NQW8-1
CNGB3ENST00000681546.1 linkuse as main transcript downstream_gene_variant

Frequencies

GnomAD3 genomes
AF:
0.591
AC:
89720
AN:
151834
Hom.:
28308
Cov.:
31
show subpopulations
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
show subpopulations
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
show subpopulations
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:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Severe early-childhood-onset retinal dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs990192; hg19: chr8-87586393; API