chr8-86739620-GTTT-G

Variant names:

• chr8-86739620-GTTT-G
• rs78198409
• NM_019098.5:c.211+32_211+34delAAA

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+32_211+34delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,485,358 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (72 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (2 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-GTTT-G is Benign according to our data. Variant chr8-86739620-GTTT-G is described in ClinVar as Benign. ClinVar VariationId is 1265940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 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+32_211+34delAAA		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+32_211+34delAAA		intron	N/A	ENSP00000316605.5	Q9NQW8-1
	CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21215_449-21213delTTT		intron	N/A
	CNGB3	ENST00000519777.1	TSL:2	n.193+32_193+34delAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2322 AN: 128852 Hom.: 72 Cov.: 0

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00502

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.0000997

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00214 AC: 2899 AN: 1356496 Hom.: 2 AF XY: 0.00196 AC XY: 1319 AN XY: 674612

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

African (AFR) AF: 0.0527 AC: 1575 AN: 29868

American (AMR) AF: 0.00617 AC: 232 AN: 37618

Ashkenazi Jewish (ASJ) AF: 0.000914 AC: 22 AN: 24076

East Asian (EAS) AF: 0.00196 AC: 73 AN: 37322

South Asian (SAS) AF: 0.00118 AC: 90 AN: 76312

European-Finnish (FIN) AF: 0.00144 AC: 61 AN: 42402

Middle Eastern (MID) AF: 0.00362 AC: 19 AN: 5254

European-Non Finnish (NFE) AF: 0.000553 AC: 579 AN: 1047570

Other (OTH) AF: 0.00442 AC: 248 AN: 56074

⚠️ 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: 0.0181 AC: 2328 AN: 128862 Hom.: 72 Cov.: 0 AF XY: 0.0175 AC XY: 1082 AN XY: 61806

African (AFR) AF: 0.0640 AC: 2229 AN: 34840

American (AMR) AF: 0.00501 AC: 65 AN: 12968

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3144

East Asian (EAS) AF: 0.00 AC: 0 AN: 4452

South Asian (SAS) AF: 0.00 AC: 0 AN: 3992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6442

Middle Eastern (MID) AF: 0.00413 AC: 1 AN: 242

European-Non Finnish (NFE) AF: 0.0000997 AC: 6 AN: 60194

Other (OTH) AF: 0.0153 AC: 27 AN: 1762

Alfa AF: 0.00442 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

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;