rs3784900

Variant names:

• chr16-57921912-A-G
• rs3784900
• NM_001297.5:c.1643+1361T>C

Variant summary

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

The NM_001297.5(CNGB1):​c.1643+1361T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,200 control chromosomes in the GnomAD database, including 2,048 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 0.15 (2048 hom., cov: 31)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.1643+1361T>C		intron_variant	Intron 18 of 32	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.1625+1361T>C		intron_variant	Intron 18 of 32		NP_001273059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.1643+1361T>C		intron_variant	Intron 18 of 32	1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5	c.1625+1361T>C		intron_variant	Intron 18 of 32	1		ENSP00000454633.1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23494 AN: 152082 Hom.: 2047 Cov.: 31

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0883

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.154 AC: 23500 AN: 152200 Hom.: 2048 Cov.: 31 AF XY: 0.157 AC XY: 11673 AN XY: 74408

African (AFR) AF: 0.0847 AC: 3517 AN: 41526

American (AMR) AF: 0.142 AC: 2174 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 702 AN: 3472

East Asian (EAS) AF: 0.0885 AC: 459 AN: 5186

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4828

European-Finnish (FIN) AF: 0.207 AC: 2194 AN: 10588

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12566 AN: 67998

Other (OTH) AF: 0.167 AC: 351 AN: 2106

Alfa AF: 0.178 Hom.: 3364

Bravo AF: 0.145

Asia WGS AF: 0.178 AC: 621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.82
PhyloP100		0.12
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: rs3784900; hg19: chr16-57955816;