rs75858066

Variant names:

• chr8-86671083-C-A
• rs75858066
• NM_019098.5:c.354G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-86671083-C-A
• chr8-86671083-C-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_019098.5(CNGB3):​c.354G>T​(p.Pro118Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00177 in 1,613,354 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P118P) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0096 (23 hom., cov: 32)
  • Exomes 𝑓: 0.00096 (17 hom.)
• Consequence: CNGB3 NM_019098.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.416
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• achromatopsia 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• CNGB3-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• cone dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• achromatopsia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• severe early-childhood-onset retinal dystrophy

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 8-86671083-C-A is Benign according to our data. Variant chr8-86671083-C-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 261088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.416 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00958 (1454/151764) while in subpopulation AFR AF = 0.0331 (1368/41366). AF 95% confidence interval is 0.0316. There are 23 homozygotes in GnomAd4. There are 700 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR,AD,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019098.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	NM_019098.5	MANE Select	c.354G>T	p.Pro118Pro	synonymous	Exon 4 of 18	NP_061971.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB3	ENST00000320005.6	TSL:1 MANE Select	c.354G>T	p.Pro118Pro	synonymous	Exon 4 of 18	ENSP00000316605.5	Q9NQW8-1
	CNGB3	ENST00000680314.1		n.115G>T		non_coding_transcript_exon	Exon 2 of 3
	CNGB3	ENST00000681746.1		n.354G>T		non_coding_transcript_exon	Exon 4 of 19	ENSP00000505959.1	A0A5J6DSN8

Frequencies

GnomAD3 genomes AF: 0.00959 AC: 1455 AN: 151646 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00408

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00623

GnomAD2 exomes AF: 0.00239 AC: 600 AN: 251238 AF XY: 0.00180

Gnomad AFR exome AF: 0.0337

Gnomad AMR exome AF: 0.00113

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000960 AC: 1403 AN: 1461590 Hom.: 17 Cov.: 32 AF XY: 0.000821 AC XY: 597 AN XY: 727120

African (AFR) AF: 0.0357 AC: 1194 AN: 33474

American (AMR) AF: 0.00127 AC: 57 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53236

Middle Eastern (MID) AF: 0.000350 AC: 2 AN: 5720

European-Non Finnish (NFE) AF: 0.0000288 AC: 32 AN: 1111972

Other (OTH) AF: 0.00181 AC: 109 AN: 60380

GnomAD4 genome AF: 0.00958 AC: 1454 AN: 151764 Hom.: 23 Cov.: 32 AF XY: 0.00944 AC XY: 700 AN XY: 74114

African (AFR) AF: 0.0331 AC: 1368 AN: 41366

American (AMR) AF: 0.00407 AC: 62 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67942

Other (OTH) AF: 0.00616 AC: 13 AN: 2110

Alfa AF: 0.00576 Hom.: 5

Bravo AF: 0.0107

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Achromatopsia (1)
-	-	1	Achromatopsia 3 (1)
-	-	1	not specified (1)
-	-	1	Severe early-childhood-onset retinal dystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.72
DANN	Benign	0.47
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs75858066; hg19: chr8-87683311;