NM_019098.5:c.211+21_211+34dupAAAAAAAAAAAAAA

Variant names:

• chr8-86739620-G-GTTTTTTTTTTTTTT
• rs78198409
• NM_019098.5:c.211+21_211+34dupAAAAAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_019098.5(CNGB3):​c.211+21_211+34dupAAAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000078 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000044 (0 hom.)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

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+21_211+34dupAAAAAAAAAAAAAA		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+35insAAAAAAAAAAAAAA		intron	N/A	ENSP00000316605.5	Q9NQW8-1
	CNGB3-AS1	ENST00000519041.1	TSL:3	n.449-21216_449-21215insTTTTTTTTTTTTTT		intron	N/A
	CNGB3	ENST00000519777.1	TSL:2	n.193+34_193+35insAAAAAAAAAAAAAA		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000776 AC: 1 AN: 128882 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000287

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000441 AC: 6 AN: 1360264 Hom.: 0 Cov.: 0 AF XY: 0.00000296 AC XY: 2 AN XY: 676430

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

African (AFR) AF: 0.00 AC: 0 AN: 29996

American (AMR) AF: 0.0000265 AC: 1 AN: 37802

Ashkenazi Jewish (ASJ) AF: 0.0000414 AC: 1 AN: 24144

East Asian (EAS) AF: 0.00 AC: 0 AN: 37496

South Asian (SAS) AF: 0.0000131 AC: 1 AN: 76466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5270

European-Non Finnish (NFE) AF: 0.00000286 AC: 3 AN: 1050228

Other (OTH) AF: 0.00 AC: 0 AN: 56278

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00308495), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00000776 AC: 1 AN: 128882 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 61802

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

African (AFR) AF: 0.0000287 AC: 1 AN: 34814

American (AMR) AF: 0.00 AC: 0 AN: 12952

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 4466

South Asian (SAS) AF: 0.00 AC: 0 AN: 4016

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 268

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 60204

Other (OTH) AF: 0.00 AC: 0 AN: 1750

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78198409; hg19: chr8-87751848;