16-57933314-T-C

Variant names:

• chr16-57933314-T-C
• rs247052
• NM_001297.5:c.1373-1436A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001297.5(CNGB1):​c.1373-1436A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 152,204 control chromosomes in the GnomAD database, including 46,196 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (46196 hom., cov: 33)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• Publications: 6 publications found

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]

CNGB1 Gene-Disease associations (from GenCC):

• CNGB1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• retinitis pigmentosa 45

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001297.5. 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
	CNGB1	NM_001297.5	MANE Select	c.1373-1436A>G		intron	N/A	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.1355-1436A>G		intron	N/A	NP_001273059.1	Q14028-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	ENST00000251102.13	TSL:1 MANE Select	c.1373-1436A>G		intron	N/A	ENSP00000251102.8	Q14028-1
	CNGB1	ENST00000564448.5	TSL:1	c.1355-1436A>G		intron	N/A	ENSP00000454633.1	Q14028-4
	CNGB1	ENST00000564654.1	TSL:4	c.224-1436A>G		intron	N/A	ENSP00000495566.1	A0A2R8Y6Y0

Frequencies

GnomAD3 genomes AF: 0.771 AC: 117286 AN: 152084 Hom.: 46132 Cov.: 33

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.702

Gnomad OTH AF: 0.739

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.771 AC: 117412 AN: 152204 Hom.: 46196 Cov.: 33 AF XY: 0.770 AC XY: 57312 AN XY: 74416

African (AFR) AF: 0.942 AC: 39130 AN: 41556

American (AMR) AF: 0.690 AC: 10552 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2449 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3782 AN: 5174

South Asian (SAS) AF: 0.813 AC: 3922 AN: 4822

European-Finnish (FIN) AF: 0.707 AC: 7490 AN: 10592

Middle Eastern (MID) AF: 0.716 AC: 209 AN: 292

European-Non Finnish (NFE) AF: 0.702 AC: 47703 AN: 67986

Other (OTH) AF: 0.741 AC: 1566 AN: 2112

Alfa AF: 0.719 Hom.: 78330

Bravo AF: 0.773

Asia WGS AF: 0.815 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.74
PhyloP100		-0.018
Mutation Taster		=100/0	polymorphism (auto)

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: rs247052; hg19: chr16-57967218;