8-86574889-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_019098.5(CNGB3):​c.*915G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 150,602 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00044 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

CNGB3
NM_019098.5 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.0230
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
Variant 8-86574889-C-G is Benign according to our data. Variant chr8-86574889-C-G is described in ClinVar as [Benign]. Clinvar id is 910388.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CNGB3NM_019098.5 linkuse as main transcriptc.*915G>C 3_prime_UTR_variant 18/18 ENST00000320005.6 NP_061971.3
CNGB3XM_011517138.3 linkuse as main transcriptc.*915G>C 3_prime_UTR_variant 16/16 XP_011515440.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CNGB3ENST00000320005.6 linkuse as main transcriptc.*915G>C 3_prime_UTR_variant 18/181 NM_019098.5 ENSP00000316605 P1Q9NQW8-1
CNGB3ENST00000517327.5 linkuse as main transcriptc.276+3800G>C intron_variant 3 ENSP00000428329
CNGB3ENST00000681546.1 linkuse as main transcriptn.3165G>C non_coding_transcript_exon_variant 13/13
CNGB3ENST00000681746.1 linkuse as main transcriptc.*1756G>C 3_prime_UTR_variant, NMD_transcript_variant 19/19 ENSP00000505959

Frequencies

GnomAD3 genomes
AF:
0.000445
AC:
67
AN:
150482
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0129
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000484
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
2
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
2
Gnomad4 NFE exome
AF:
0.00
GnomAD4 genome
AF:
0.000445
AC:
67
AN:
150602
Hom.:
1
Cov.:
32
AF XY:
0.000394
AC XY:
29
AN XY:
73578
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.0129
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.000125

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Severe early-childhood-onset retinal dystrophy Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -
Achromatopsia 3 Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaApr 27, 2017This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
13
DANN
Benign
0.70

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: rs189446254; hg19: chr8-87587117; API