16-57933314-T-C

Position:

• chr16-57933314-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.1373-1436A>G		intron_variant		ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.1355-1436A>G		intron_variant			NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.1373-1436A>G		intron_variant		1	NM_001297.5	ENSP00000251102	P4
CNGB1	ENST00000564448.5	c.1355-1436A>G		intron_variant		1		ENSP00000454633	A2
CNGB1	ENST00000564654.1	c.224-1436A>G		intron_variant		4		ENSP00000495566
CNGB1	ENST00000564450.1	n.120+6116A>G		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.942

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.813

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.702

Gnomad4 OTH AF: 0.741

Alfa AF: 0.710 Hom.: 52864

Bravo AF: 0.773

Asia WGS AF: 0.815 AC: 2834 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.9
DANN	Benign	0.74

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: rs247052; hg19: chr16-57967218;