rs79889567

Variant names:

• chr16-57901566-C-T
• rs79889567
• NM_001297.5:c.2854G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001297.5(CNGB1):​c.2854G>A​(p.Val952Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,112 control chromosomes in the GnomAD database, including 175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (57 hom., cov: 32)
  • Exomes 𝑓: 0.011 (118 hom.)
• Consequence: CNGB1 NM_001297.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 7.88
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011026382).
• BP6: Variant 16-57901566-C-T is Benign according to our data. Variant chr16-57901566-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0204 (3105/152252) while in subpopulation AFR AF = 0.0486 (2021/41546). AF 95% confidence interval is 0.0469. There are 57 homozygotes in GnomAd4. There are 1440 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR,AD gene

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.2854G>A	p.Val952Met	missense	Exon 28 of 33	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.2836G>A	p.Val946Met	missense	Exon 28 of 33	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.2854G>A	p.Val952Met	missense	Exon 28 of 33	ENSP00000251102.8	Q14028-1
	CNGB1	ENST00000564448.5	TSL:1	c.2836G>A	p.Val946Met	missense	Exon 28 of 33	ENSP00000454633.1	Q14028-4
	CNGB1	ENST00000569643.1	TSL:5	n.511G>A		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3101 AN: 152134 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00871

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00660

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0111

Gnomad OTH AF: 0.0248

GnomAD2 exomes AF: 0.0108 AC: 2707 AN: 249550 AF XY: 0.00962

Gnomad AFR exome AF: 0.0504

Gnomad AMR exome AF: 0.00504

Gnomad ASJ exome AF: 0.0166

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00923

Gnomad NFE exome AF: 0.0112

Gnomad OTH exome AF: 0.0117

GnomAD4 exome AF: 0.0110 AC: 16126 AN: 1461860 Hom.: 118 Cov.: 33 AF XY: 0.0106 AC XY: 7729 AN XY: 727230

African (AFR) AF: 0.0485 AC: 1624 AN: 33478

American (AMR) AF: 0.00579 AC: 259 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0170 AC: 444 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.00184 AC: 159 AN: 86258

European-Finnish (FIN) AF: 0.00891 AC: 476 AN: 53416

Middle Eastern (MID) AF: 0.0314 AC: 181 AN: 5762

European-Non Finnish (NFE) AF: 0.0110 AC: 12219 AN: 1112000

Other (OTH) AF: 0.0126 AC: 762 AN: 60386

GnomAD4 genome AF: 0.0204 AC: 3105 AN: 152252 Hom.: 57 Cov.: 32 AF XY: 0.0193 AC XY: 1440 AN XY: 74426

African (AFR) AF: 0.0486 AC: 2021 AN: 41546

American (AMR) AF: 0.00869 AC: 133 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4812

European-Finnish (FIN) AF: 0.00660 AC: 70 AN: 10606

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 756 AN: 68018

Other (OTH) AF: 0.0246 AC: 52 AN: 2116

Alfa AF: 0.0143 Hom.: 104

Bravo AF: 0.0220

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.0479 AC: 199

ESP6500EA AF: 0.00853 AC: 72

ExAC AF: 0.0114 AC: 1384

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0109

EpiControl AF: 0.0110

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa 45 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.062	T
BayesDel_noAF	Pathogenic	0.18
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
MetaRNN	Benign	0.011	T
MetaSVM	Uncertain	-0.075	T
MutationAssessor	Benign	1.9	M
PhyloP100		7.9
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.77
Sift	Uncertain	0.025	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.29
MPC		0.28
ClinPred		0.020	T
GERP RS		4.6
PromoterAI		0.0051	Neutral
Varity_R		0.21
gMVP		0.44
Mutation Taster		=92/8	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: rs79889567; hg19: chr16-57935470;