16-57882936-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001297.5(CNGB1):c.*1228C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,176 control chromosomes in the GnomAD database, including 297 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.051 (297 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNGB1 NM_001297.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.749

Genes affected

CNGB1 (HGNC:2151): (cyclic nucleotide gated channel subunit beta 1) In humans, the rod photoreceptor cGMP-gated cation channel helps regulate ion flow into the rod photoreceptor outer segment in response to light-induced alteration of the levels of intracellular cGMP. This channel consists of two subunits, alpha and beta, with the protein encoded by this gene representing the beta subunit. Defects in this gene are a cause of cause of retinitis pigmentosa type 45. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-57882936-G-C is Benign according to our data. Variant chr16-57882936-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 320029.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB1	NM_001297.5	c.*1228C>G		3_prime_UTR_variant	33/33	ENST00000251102.13
CNGB1	NM_001286130.2	c.*1228C>G		3_prime_UTR_variant	33/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB1	ENST00000251102.13	c.*1228C>G		3_prime_UTR_variant	33/33	1	NM_001297.5	P4

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7834 AN: 152058 Hom.: 298 Cov.: 31

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0637

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.0532

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

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0515 AC: 7830 AN: 152176 Hom.: 297 Cov.: 31 AF XY: 0.0496 AC XY: 3686 AN XY: 74378

Gnomad4 AFR AF: 0.0145

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.0761

Gnomad4 OTH AF: 0.0526

Alfa AF: 0.0575 Hom.: 37

Bravo AF: 0.0498

Asia WGS AF: 0.0110 AC: 40 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis pigmentosa Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.75
Dann	Benign	0.63

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: rs1477406; hg19: chr16-57916840;