16-57959985-G-T

Variant names:

• chr16-57959985-G-T
• rs750620302
• NM_001297.5:c.664C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001297.5(CNGB1):​c.664C>A​(p.Gln222Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNGB1 NM_001297.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07049483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNGB1	NM_001297.5	c.664C>A	p.Gln222Lys	missense_variant	Exon 10 of 33	ENST00000251102.13	NP_001288.3
CNGB1	NM_001286130.2	c.646C>A	p.Gln216Lys	missense_variant	Exon 10 of 33		NP_001273059.1
CNGB1	NM_001135639.2	c.664C>A	p.Gln222Lys	missense_variant	Exon 10 of 13		NP_001129111.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGB1	ENST00000251102.13	c.664C>A	p.Gln222Lys	missense_variant	Exon 10 of 33	1	NM_001297.5	ENSP00000251102.8
CNGB1	ENST00000564448.5	c.646C>A	p.Gln216Lys	missense_variant	Exon 10 of 33	1		ENSP00000454633.1
CNGB1	ENST00000311183.8	c.664C>A	p.Gln222Lys	missense_variant	Exon 10 of 13	1		ENSP00000311670.4
CNGB1	ENST00000562761.1	c.*21C>A		downstream_gene_variant		3		ENSP00000455708.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000476 AC: 1 AN: 210288 AF XY: 0.00

Gnomad AFR exome AF: 0.0000798

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1438284 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 712726

African (AFR) AF: 0.00 AC: 0 AN: 33262

American (AMR) AF: 0.00 AC: 0 AN: 41222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25394

East Asian (EAS) AF: 0.00 AC: 0 AN: 39034

South Asian (SAS) AF: 0.00 AC: 0 AN: 82618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4820

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101246

Other (OTH) AF: 0.00 AC: 0 AN: 59420

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152114 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74296

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68002

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000833 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.5
DANN	Benign	0.61
DEOGEN2	Benign	0.097	T;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.070	T;T;T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.0	N;.;N
PhyloP100		-0.14
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.32	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.13
MutPred		0.36		Gain of methylation at Q222 (P = 6e-04);.;Gain of methylation at Q222 (P = 6e-04);
MVP		0.69
MPC		0.12
ClinPred		0.016	T
GERP RS		-0.88
Varity_R		0.071
gMVP		0.049

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: rs750620302; hg19: chr16-57993889;