8-86739620-GTTTTTT-GTTTTT

Variant names:

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

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+34delA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.36 (7096 hom., cov: 0)
  • Exomes 𝑓: 0.31 (316 hom.)
  • Failed GnomAD Quality Control
• 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-GT-G is Benign according to our data. Variant chr8-86739620-GT-G is described in ClinVar as Benign. ClinVar VariationId is 1233884.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.395 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+34delA		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+34delA		intron	N/A	ENSP00000316605.5	Q9NQW8-1
	CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21215delT		intron	N/A
	CNGB3	ENST00000519777.1	TSL:2	n.193+34delA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.361 AC: 46359 AN: 128534 Hom.: 7108 Cov.: 0

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.349

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.284

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.344

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.306 AC: 407716 AN: 1332888 Hom.: 316 Cov.: 0 AF XY: 0.304 AC XY: 201331 AN XY: 662412

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

African (AFR) AF: 0.252 AC: 7424 AN: 29410

American (AMR) AF: 0.276 AC: 10155 AN: 36772

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 6602 AN: 23614

East Asian (EAS) AF: 0.278 AC: 10129 AN: 36462

South Asian (SAS) AF: 0.267 AC: 19965 AN: 74734

European-Finnish (FIN) AF: 0.295 AC: 12241 AN: 41530

Middle Eastern (MID) AF: 0.285 AC: 1458 AN: 5114

European-Non Finnish (NFE) AF: 0.314 AC: 323141 AN: 1030112

Other (OTH) AF: 0.301 AC: 16601 AN: 55140

⚠️ 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: 0.360 AC: 46339 AN: 128544 Hom.: 7096 Cov.: 0 AF XY: 0.359 AC XY: 22149 AN XY: 61660

African (AFR) AF: 0.309 AC: 10748 AN: 34754

American (AMR) AF: 0.380 AC: 4920 AN: 12944

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1137 AN: 3136

East Asian (EAS) AF: 0.349 AC: 1549 AN: 4440

South Asian (SAS) AF: 0.411 AC: 1637 AN: 3982

European-Finnish (FIN) AF: 0.338 AC: 2180 AN: 6450

Middle Eastern (MID) AF: 0.281 AC: 68 AN: 242

European-Non Finnish (NFE) AF: 0.388 AC: 23261 AN: 60014

Other (OTH) AF: 0.342 AC: 602 AN: 1758

Alfa AF: 0.180 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: COSV60686022;