chr8-86739620-G-GT

Variant names:

• chr8-86739620-G-GT
• rs78198409
• NM_019098.5:c.211+34dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019098.5(CNGB3):​c.211+34dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.038 (265 hom., cov: 0)
  • Exomes 𝑓: 0.14 (15 hom.)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129
• 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: 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)

CNGB3-AS1 (HGNC:58258):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-86739620-G-GT is Benign according to our data. Variant chr8-86739620-G-GT is described in ClinVar as Benign. ClinVar VariationId is 1183444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019098.5. 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.211+34dupA		intron	N/A	NP_061971.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	ENST00000320005.6	TSL:1 MANE Select	c.211+34_211+35insA		intron	N/A	ENSP00000316605.5	Q9NQW8-1
	CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21216_449-21215insT		intron	N/A
	CNGB3	ENST00000519777.1	TSL:2	n.193+34_193+35insA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0381 AC: 4902 AN: 128824 Hom.: 265 Cov.: 0

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0176

Gnomad ASJ AF: 0.00763

Gnomad EAS AF: 0.00134

Gnomad SAS AF: 0.00299

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0224

Gnomad NFE AF: 0.00562

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.135 AC: 176248 AN: 1304352 Hom.: 15 Cov.: 0 AF XY: 0.136 AC XY: 88179 AN XY: 647800

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.156 AC: 4498 AN: 28920

American (AMR) AF: 0.112 AC: 4089 AN: 36422

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3363 AN: 23064

East Asian (EAS) AF: 0.117 AC: 4192 AN: 35982

South Asian (SAS) AF: 0.151 AC: 10888 AN: 72262

European-Finnish (FIN) AF: 0.125 AC: 5073 AN: 40680

Middle Eastern (MID) AF: 0.122 AC: 618 AN: 5082

European-Non Finnish (NFE) AF: 0.135 AC: 136316 AN: 1007886

Other (OTH) AF: 0.133 AC: 7211 AN: 54054

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0380 AC: 4898 AN: 128834 Hom.: 265 Cov.: 0 AF XY: 0.0381 AC XY: 2353 AN XY: 61792

African (AFR) AF: 0.119 AC: 4162 AN: 34836

American (AMR) AF: 0.0176 AC: 228 AN: 12964

Ashkenazi Jewish (ASJ) AF: 0.00763 AC: 24 AN: 3144

East Asian (EAS) AF: 0.00135 AC: 6 AN: 4452

South Asian (SAS) AF: 0.00276 AC: 11 AN: 3992

European-Finnish (FIN) AF: 0.0104 AC: 67 AN: 6446

Middle Eastern (MID) AF: 0.0248 AC: 6 AN: 242

European-Non Finnish (NFE) AF: 0.00562 AC: 338 AN: 60170

Other (OTH) AF: 0.0318 AC: 56 AN: 1762

Alfa AF: 0.0752 Hom.: 244

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
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: rs78198409; hg19: chr8-87751848; COSMIC: COSV60698905;