rs1458118

Positions:

• chr8-86704055-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019098.5(CNGB3):​c.338+22476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,004 control chromosomes in the GnomAD database, including 7,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (7129 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.715

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.338+22476G>A		intron_variant		ENST00000320005.6	NP_061971.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.338+22476G>A		intron_variant		1	NM_019098.5	ENSP00000316605	P1
CNGB3	ENST00000519777.1	n.668G>A		non_coding_transcript_exon_variant	4/4	2
CNGB3	ENST00000681746.1	c.338+22476G>A		intron_variant, NMD_transcript_variant				ENSP00000505959

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45112 AN: 151886 Hom.: 7129 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.271

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.297 AC: 45136 AN: 152004 Hom.: 7129 Cov.: 32 AF XY: 0.301 AC XY: 22350 AN XY: 74286

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.231

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.269

Alfa AF: 0.243 Hom.: 4657

Bravo AF: 0.304

Asia WGS AF: 0.374 AC: 1301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs1458118; hg19: chr8-87716283;