8-86739642-A-C

Variant names:

• chr8-86739642-A-C
• rs66881636
• NM_019098.5:c.211+13T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_019098.5(CNGB3):​c.211+13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0373 in 1,565,710 control chromosomes in the GnomAD database, including 1,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (204 hom., cov: 29)
  • Exomes 𝑓: 0.036 (1340 hom.)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.564
• Publications: 6 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: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia
• 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)

ENSG00000253778 (HGNC:58258):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 8-86739642-A-C is Benign according to our data. Variant chr8-86739642-A-C is described in ClinVar as [Benign]. Clinvar id is 261086.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.211+13T>G		intron_variant	Intron 2 of 17	ENST00000320005.6	NP_061971.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.211+13T>G		intron_variant	Intron 2 of 17	1	NM_019098.5	ENSP00000316605.5

Frequencies

GnomAD3 genomes AF: 0.0491 AC: 6875 AN: 139930 Hom.: 205 Cov.: 29

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0705

Gnomad ASJ AF: 0.0650

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0434

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0308

Gnomad OTH AF: 0.0675

GnomAD2 exomes AF: 0.0566 AC: 13087 AN: 231144 AF XY: 0.0549

Gnomad AFR exome AF: 0.0602

Gnomad AMR exome AF: 0.0902

Gnomad ASJ exome AF: 0.0618

Gnomad EAS exome AF: 0.143

Gnomad FIN exome AF: 0.0514

Gnomad NFE exome AF: 0.0352

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0361 AC: 51502 AN: 1425742 Hom.: 1340 Cov.: 44 AF XY: 0.0365 AC XY: 25854 AN XY: 709158

African (AFR) AF: 0.0602 AC: 1884 AN: 31282

American (AMR) AF: 0.0864 AC: 3407 AN: 39424

Ashkenazi Jewish (ASJ) AF: 0.0581 AC: 1469 AN: 25272

East Asian (EAS) AF: 0.121 AC: 4749 AN: 39224

South Asian (SAS) AF: 0.0454 AC: 3671 AN: 80888

European-Finnish (FIN) AF: 0.0518 AC: 2550 AN: 49212

Middle Eastern (MID) AF: 0.0798 AC: 443 AN: 5552

European-Non Finnish (NFE) AF: 0.0281 AC: 30749 AN: 1096152

Other (OTH) AF: 0.0439 AC: 2580 AN: 58736

GnomAD4 genome AF: 0.0491 AC: 6877 AN: 139968 Hom.: 204 Cov.: 29 AF XY: 0.0527 AC XY: 3547 AN XY: 67274

African (AFR) AF: 0.0583 AC: 2148 AN: 36842

American (AMR) AF: 0.0708 AC: 968 AN: 13678

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 222 AN: 3414

East Asian (EAS) AF: 0.134 AC: 656 AN: 4886

South Asian (SAS) AF: 0.0430 AC: 194 AN: 4510

European-Finnish (FIN) AF: 0.0649 AC: 506 AN: 7798

Middle Eastern (MID) AF: 0.112 AC: 29 AN: 260

European-Non Finnish (NFE) AF: 0.0309 AC: 2029 AN: 65768

Other (OTH) AF: 0.0649 AC: 125 AN: 1926

Alfa AF: 0.0363 Hom.: 174

Bravo AF: 0.0499

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Achromatopsia 3 Benign:2

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Severe early-childhood-onset retinal dystrophy Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.1
DANN	Benign	0.83
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs66881636; hg19: chr8-87751870; COSMIC: COSV60690329;