16-57903952-G-T

Variant names:

• chr16-57903952-G-T
• rs413562
• NM_001297.5:c.2664C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001297.5(CNGB1):​c.2664C>A​(p.Ala888Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,613,682 control chromosomes in the GnomAD database, including 11,404 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A888A) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.15 (1967 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9437 hom.)
• Consequence: CNGB1 NM_001297.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -8.35
• Publications: 19 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 16-57903952-G-T is Benign according to our data. Variant chr16-57903952-G-T is described in ClinVar as Benign. ClinVar VariationId is 93700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 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.2664C>A	p.Ala888Ala	synonymous	Exon 27 of 33	NP_001288.3
	CNGB1	NM_001286130.2		c.2646C>A	p.Ala882Ala	synonymous	Exon 27 of 33	NP_001273059.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	ENST00000251102.13	TSL:1 MANE Select	c.2664C>A	p.Ala888Ala	synonymous	Exon 27 of 33	ENSP00000251102.8
	CNGB1	ENST00000564448.5	TSL:1	c.2646C>A	p.Ala882Ala	synonymous	Exon 27 of 33	ENSP00000454633.1
	CNGB1	ENST00000569643.1	TSL:5	n.321C>A		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22158 AN: 152064 Hom.: 1964 Cov.: 33

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0940

Gnomad EAS AF: 0.0825

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0484

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.133

GnomAD2 exomes AF: 0.117 AC: 29178 AN: 248746 AF XY: 0.113

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.0909

Gnomad EAS exome AF: 0.0818

Gnomad FIN exome AF: 0.0523

Gnomad NFE exome AF: 0.103

Gnomad OTH exome AF: 0.104

GnomAD4 exome AF: 0.108 AC: 158551 AN: 1461500 Hom.: 9437 Cov.: 55 AF XY: 0.108 AC XY: 78517 AN XY: 727052

African (AFR) AF: 0.261 AC: 8741 AN: 33470

American (AMR) AF: 0.160 AC: 7156 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 2448 AN: 26130

East Asian (EAS) AF: 0.0642 AC: 2549 AN: 39698

South Asian (SAS) AF: 0.118 AC: 10176 AN: 86240

European-Finnish (FIN) AF: 0.0536 AC: 2861 AN: 53398

Middle Eastern (MID) AF: 0.118 AC: 673 AN: 5688

European-Non Finnish (NFE) AF: 0.105 AC: 117240 AN: 1111802

Other (OTH) AF: 0.111 AC: 6707 AN: 60372

GnomAD4 genome AF: 0.146 AC: 22200 AN: 152182 Hom.: 1967 Cov.: 33 AF XY: 0.142 AC XY: 10591 AN XY: 74390

African (AFR) AF: 0.254 AC: 10547 AN: 41514

American (AMR) AF: 0.148 AC: 2265 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0940 AC: 326 AN: 3468

East Asian (EAS) AF: 0.0819 AC: 423 AN: 5166

South Asian (SAS) AF: 0.125 AC: 601 AN: 4820

European-Finnish (FIN) AF: 0.0484 AC: 513 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7171 AN: 68012

Other (OTH) AF: 0.134 AC: 283 AN: 2112

Alfa AF: 0.105 Hom.: 3683

EpiCase AF: 0.100

EpiControl AF: 0.101

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)
-	-	1	Retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.030
DANN	Benign	0.31
PhyloP100		-8.4
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: rs413562; hg19: chr16-57937856;