8-86654018-TTTTGTAGAAGT-TT

Position:

• chr8-86654018-TTTTGTAGAAGT-TT

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_019098.5(CNGB3):​c.887_896delCTTCTACAAA​(p.Thr296fs) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in Lovd as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNGB3 NM_019098.5 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.62

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 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 8-86654018-TTTTGTAGAAG-T is Pathogenic according to our data. Variant chr8-86654018-TTTTGTAGAAG-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.887_896delCTTCTACAAA	p.Thr296fs	frameshift_variant	7/18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.473_482delCTTCTACAAA	p.Thr158fs	frameshift_variant	5/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.887_896delCTTCTACAAA	p.Thr296fs	frameshift_variant	7/18	1	NM_019098.5	ENSP00000316605.5
CNGB3	ENST00000681546.1	n.707_716delCTTCTACAAA		non_coding_transcript_exon_variant	2/13
CNGB3	ENST00000681746.1	n.887_896delCTTCTACAAA		non_coding_transcript_exon_variant	7/19			ENSP00000505959.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs886063161; hg19: chr8-87666246;