rs3217489

Variant names:

• chr8-86574893-CAT-C
• rs3217489
• NM_019098.5:c.*909_*910delAT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_019098.5(CNGB3):​c.*909_*910delAT 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
• 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), PanelApp Australia
• 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 -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 VariationId 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.

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.*909_*910delAT		3_prime_UTR	Exon 18 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.*909_*910delAT		3_prime_UTR	Exon 18 of 18	ENSP00000316605.5	Q9NQW8-1
	CNGB3	ENST00000517327.5	TSL:3	c.276+3794_276+3795delAT		intron	N/A	ENSP00000428329.1	H0YAZ4
	CNGB3	ENST00000681546.1		n.3159_3160delAT		non_coding_transcript_exon	Exon 13 of 13

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0791 AC: 3284 AN: 41506

American (AMR) AF: 0.0611 AC: 933 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0622 AC: 216 AN: 3470

East Asian (EAS) AF: 0.0998 AC: 517 AN: 5182

South Asian (SAS) AF: 0.0759 AC: 366 AN: 4824

European-Finnish (FIN) AF: 0.108 AC: 1143 AN: 10570

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0898 AC: 6109 AN: 68010

Other (OTH) AF: 0.0773 AC: 163 AN: 2110

Alfa AF: 0.0967 Hom.: 80

Bravo AF: 0.0817

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Achromatopsia (1)
-	-	1	Stargardt Disease, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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