chr8-86578666-G-C

Variant names:

• chr8-86578666-G-C
• rs41466745
• NM_019098.5:c.2103+23C>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.2103+23C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 1,611,896 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (337 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (341 hom.)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.316
• Publications: 2 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-86578666-G-C is Benign according to our data. Variant chr8-86578666-G-C is described in ClinVar as Benign. ClinVar VariationId is 261085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.2103+23C>G		intron_variant	Intron 17 of 17	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.1689+23C>G		intron_variant	Intron 15 of 15		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.2103+23C>G		intron_variant	Intron 17 of 17	1	NM_019098.5	ENSP00000316605.5
CNGB3	ENST00000517327.5	c.276+23C>G		intron_variant	Intron 2 of 3	3		ENSP00000428329.1
CNGB3	ENST00000681546.1	n.1923+23C>G		intron_variant	Intron 12 of 12
CNGB3	ENST00000681746.1	n.*514+23C>G		intron_variant	Intron 18 of 18			ENSP00000505959.1

Frequencies

GnomAD3 genomes AF: 0.0393 AC: 5977 AN: 152084 Hom.: 333 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0133

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00238

Gnomad OTH AF: 0.0402

GnomAD2 exomes AF: 0.0134 AC: 3351 AN: 250902 AF XY: 0.0113

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.0246

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.000740

Gnomad NFE exome AF: 0.00217

Gnomad OTH exome AF: 0.00996

GnomAD4 exome AF: 0.00658 AC: 9612 AN: 1459694 Hom.: 341 Cov.: 31 AF XY: 0.00644 AC XY: 4677 AN XY: 726254

African (AFR) AF: 0.129 AC: 4317 AN: 33398

American (AMR) AF: 0.0110 AC: 492 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0250 AC: 654 AN: 26122

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39682

South Asian (SAS) AF: 0.0131 AC: 1131 AN: 86182

European-Finnish (FIN) AF: 0.000750 AC: 40 AN: 53368

Middle Eastern (MID) AF: 0.0158 AC: 80 AN: 5048

European-Non Finnish (NFE) AF: 0.00185 AC: 2051 AN: 1110926

Other (OTH) AF: 0.0140 AC: 842 AN: 60254

GnomAD4 genome AF: 0.0394 AC: 5997 AN: 152202 Hom.: 337 Cov.: 32 AF XY: 0.0385 AC XY: 2867 AN XY: 74410

African (AFR) AF: 0.127 AC: 5268 AN: 41526

American (AMR) AF: 0.0200 AC: 306 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5164

South Asian (SAS) AF: 0.0133 AC: 64 AN: 4816

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10608

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.00238 AC: 162 AN: 68018

Other (OTH) AF: 0.0417 AC: 88 AN: 2110

Alfa AF: 0.00524 Hom.: 4

Bravo AF: 0.0444

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jul 05, 2018

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

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.32
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: rs41466745; hg19: chr8-87590894;