rs1554611763

Positions:

• chr8-86643876-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000320005.6(CNGB3):​c.1056-3C>G variant causes a splice region, splice polypyrimidine tract, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CNGB3 ENST00000320005.6 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 6.11

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.1056-3C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.642-3C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.1056-3C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_019098.5	ENSP00000316605	P1
CNGB3	ENST00000681746.1	c.1056-3C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant				ENSP00000505959
CNGB3	ENST00000681546.1	n.876-3C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Achromatopsia 3 Uncertain:1

Uncertain significance, no assertion criteria provided

research

Molecular Genetics Laboratory, Institute for Ophthalmic Research

Mar 27, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.94
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.97		Position offset: -3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1554611763; hg19: chr8-87656104;