8-86739620-GTTTTTT-GTTT

Variant names:

• chr8-86739620-GTTT-G
• rs78198409
• NM_019098.5:c.211+32_211+34delAAA

Variant summary

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

The NM_019098.5(CNGB3):​c.211+32_211+34delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00352 in 1,485,358 control chromosomes in the GnomAD database, including 74 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (72 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (2 hom.)
• Consequence: CNGB3 NM_019098.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.129

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]

ENSG00000254115 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-86739620-GTTT-G is Benign according to our data. Variant chr8-86739620-GTTT-G is described in ClinVar as [Benign]. Clinvar id is 1265940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB3	NM_019098.5	c.211+32_211+34delAAA		intron_variant	Intron 2 of 17	ENST00000320005.6	NP_061971.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB3	ENST00000320005.6	c.211+32_211+34delAAA		intron_variant	Intron 2 of 17	1	NM_019098.5	ENSP00000316605.5
ENSG00000254115	ENST00000519041.1	n.449-21215_449-21213delTTT		intron_variant	Intron 1 of 2	3
CNGB3	ENST00000519777.1	n.193+32_193+34delAAA		intron_variant	Intron 2 of 3	2
CNGB3	ENST00000681746.1	n.211+32_211+34delAAA		intron_variant	Intron 2 of 18			ENSP00000505959.1

Frequencies

GnomAD3 genomes AF: 0.0180 AC: 2322 AN: 128852 Hom.: 72 Cov.: 0

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00502

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00373

Gnomad NFE AF: 0.0000997

Gnomad OTH AF: 0.0154

GnomAD4 exome AF: 0.00214 AC: 2899 AN: 1356496 Hom.: 2 AF XY: 0.00196 AC XY: 1319 AN XY: 674612

Gnomad4 AFR exome AF: 0.0527

Gnomad4 AMR exome AF: 0.00617

Gnomad4 ASJ exome AF: 0.000914

Gnomad4 EAS exome AF: 0.00196

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.000553

Gnomad4 OTH exome AF: 0.00442

GnomAD4 genome AF: 0.0181 AC: 2328 AN: 128862 Hom.: 72 Cov.: 0 AF XY: 0.0175 AC XY: 1082 AN XY: 61806

Gnomad4 AFR AF: 0.0640

Gnomad4 AMR AF: 0.00501

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000997

Gnomad4 OTH AF: 0.0153

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs78198409; hg19: chr8-87751848;