8-86574893-CAT-C

Position:

• chr8-86574893-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019098.5(CNGB3):​c.*909_*910del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0843 in 152,158 control chromosomes in the GnomAD database, including 578 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.084 (578 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNGB3 NM_019098.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.405

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 -10 ACMG points.

• BP6: Variant 8-86574893-CAT-C is Benign according to our data. Variant chr8-86574893-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 363853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.*909_*910del		3_prime_UTR_variant	18/18	ENST00000320005.6	NP_061971.3
CNGB3	XM_011517138.3	c.*909_*910del		3_prime_UTR_variant	16/16		XP_011515440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.*909_*910del		3_prime_UTR_variant	18/18	1	NM_019098.5	ENSP00000316605	P1
CNGB3	ENST00000517327.5	c.276+3794_276+3795del		intron_variant		3		ENSP00000428329
CNGB3	ENST00000681546.1	n.3159_3160del		non_coding_transcript_exon_variant	13/13
CNGB3	ENST00000681746.1	c.*1750_*1751del		3_prime_UTR_variant, NMD_transcript_variant	19/19			ENSP00000505959

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12806 AN: 152040 Hom.: 579 Cov.: 31

Gnomad AFR AF: 0.0791

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.0611

Gnomad ASJ AF: 0.0622

Gnomad EAS AF: 0.0995

Gnomad SAS AF: 0.0748

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.0766

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0843 AC: 12824 AN: 152158 Hom.: 578 Cov.: 31 AF XY: 0.0849 AC XY: 6316 AN XY: 74378

Gnomad4 AFR AF: 0.0791

Gnomad4 AMR AF: 0.0611

Gnomad4 ASJ AF: 0.0622

Gnomad4 EAS AF: 0.0998

Gnomad4 SAS AF: 0.0759

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0898

Gnomad4 OTH AF: 0.0773

Alfa AF: 0.0967 Hom.: 80

Bravo AF: 0.0817

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Stargardt Disease, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Achromatopsia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3217489; hg19: chr8-87587121; COSMIC: COSV60683935;