8-86592903-T-C

Variant names:

• chr8-86592903-T-C
• rs1992405
• NM_019098.5:c.1781+11190A>G

Variant summary

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

The NM_019098.5(CNGB3):​c.1781+11190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 152,068 control chromosomes in the GnomAD database, including 34,652 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 0.65 (34652 hom., cov: 33)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.1781+11190A>G		intron_variant	Intron 15 of 17	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.1367+11190A>G		intron_variant	Intron 13 of 15		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.1781+11190A>G		intron_variant	Intron 15 of 17	1	NM_019098.5	ENSP00000316605.5
CNGB3	ENST00000681546.1	n.1601+11190A>G		intron_variant	Intron 10 of 12
CNGB3	ENST00000681746.1	n.*192+11190A>G		intron_variant	Intron 16 of 18			ENSP00000505959.1

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98889 AN: 151950 Hom.: 34647 Cov.: 33

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.757

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.650 AC: 98916 AN: 152068 Hom.: 34652 Cov.: 33 AF XY: 0.651 AC XY: 48371 AN XY: 74350

Gnomad4 AFR AF: 0.374

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.643

Alfa AF: 0.755 Hom.: 66443

Bravo AF: 0.637

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.8
DANN	Benign	0.71

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: rs1992405; hg19: chr8-87605131;