16-57903952-G-C

Variant names:

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

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>G​(p.Ala888Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,613,534 control chromosomes in the GnomAD database, including 470,130 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 0.68 (37045 hom., cov: 33)
  • Exomes 𝑓: 0.77 (433085 hom.)
• Consequence: CNGB1 NM_001297.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• 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-C is Benign according to our data. Variant chr16-57903952-G-C is described in ClinVar as Benign. ClinVar VariationId is 166894.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 (EAS) allele frequency at 95% confidence interval = 0.896 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>G	p.Ala888Ala	synonymous	Exon 27 of 33	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.2646C>G	p.Ala882Ala	synonymous	Exon 27 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.2664C>G	p.Ala888Ala	synonymous	Exon 27 of 33	ENSP00000251102.8	Q14028-1
	CNGB1	ENST00000564448.5	TSL:1	c.2646C>G	p.Ala882Ala	synonymous	Exon 27 of 33	ENSP00000454633.1	Q14028-4
	CNGB1	ENST00000569643.1	TSL:5	n.321C>G		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103729 AN: 152092 Hom.: 37041 Cov.: 33

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.891

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.830

Gnomad FIN AF: 0.809

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.711

GnomAD2 exomes AF: 0.765 AC: 190370 AN: 248746 AF XY: 0.773

Gnomad AFR exome AF: 0.438

Gnomad AMR exome AF: 0.762

Gnomad ASJ exome AF: 0.700

Gnomad EAS exome AF: 0.918

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.766

Gnomad OTH exome AF: 0.760

GnomAD4 exome AF: 0.767 AC: 1120710 AN: 1461324 Hom.: 433085 Cov.: 55 AF XY: 0.770 AC XY: 559583 AN XY: 726942

African (AFR) AF: 0.437 AC: 14620 AN: 33470

American (AMR) AF: 0.761 AC: 34004 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 18101 AN: 26130

East Asian (EAS) AF: 0.936 AC: 37141 AN: 39698

South Asian (SAS) AF: 0.830 AC: 71555 AN: 86238

European-Finnish (FIN) AF: 0.817 AC: 43622 AN: 53394

Middle Eastern (MID) AF: 0.688 AC: 3912 AN: 5688

European-Non Finnish (NFE) AF: 0.767 AC: 852456 AN: 1111658

Other (OTH) AF: 0.751 AC: 45299 AN: 60356

GnomAD4 genome AF: 0.682 AC: 103771 AN: 152210 Hom.: 37045 Cov.: 33 AF XY: 0.689 AC XY: 51248 AN XY: 74402

African (AFR) AF: 0.444 AC: 18439 AN: 41522

American (AMR) AF: 0.744 AC: 11372 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2395 AN: 3468

East Asian (EAS) AF: 0.918 AC: 4740 AN: 5166

South Asian (SAS) AF: 0.829 AC: 3998 AN: 4824

European-Finnish (FIN) AF: 0.809 AC: 8571 AN: 10600

Middle Eastern (MID) AF: 0.636 AC: 187 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51750 AN: 68016

Other (OTH) AF: 0.712 AC: 1506 AN: 2114

Alfa AF: 0.714 Hom.: 3683

EpiCase AF: 0.755

EpiControl AF: 0.762

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	3	not provided (3)
-	-	2	Retinitis pigmentosa 45 (2)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.035
DANN	Benign	0.33
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; COSMIC: COSV108028896; COSMIC: COSV108028896;