rs437920

Variant names:

• chr16-57903991-G-A
• rs437920
• NM_001297.5:c.2635-10C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-57903991-G-A
• chr16-57903991-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001297.5(CNGB1):​c.2635-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.832 in 1,611,120 control chromosomes in the GnomAD database, including 560,897 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.78 (46809 hom., cov: 32)
  • Exomes 𝑓: 0.84 (514088 hom.)
• Consequence: CNGB1 NM_001297.5 intron
• Scores: Splicing: ADA: 0.00001391
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.181
• Publications: 13 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 (BayesDel_noAF=-0.86).
• BP6: Variant 16-57903991-G-A is Benign according to our data. Variant chr16-57903991-G-A is described in ClinVar as Benign. ClinVar VariationId is 166895.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.856 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.2635-10C>T		intron	N/A	NP_001288.3
	CNGB1	NM_001286130.2		c.2617-10C>T		intron	N/A	NP_001273059.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGB1	ENST00000251102.13	TSL:1 MANE Select	c.2635-10C>T		intron	N/A	ENSP00000251102.8
	CNGB1	ENST00000564448.5	TSL:1	c.2617-10C>T		intron	N/A	ENSP00000454633.1
	CNGB1	ENST00000569643.1	TSL:5	n.292-10C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118400 AN: 151902 Hom.: 46783 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.915

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.829

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.848

Gnomad OTH AF: 0.802

GnomAD2 exomes AF: 0.812 AC: 200545 AN: 246984 AF XY: 0.822

Gnomad AFR exome AF: 0.661

Gnomad AMR exome AF: 0.763

Gnomad ASJ exome AF: 0.787

Gnomad EAS exome AF: 0.657

Gnomad FIN exome AF: 0.841

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.813

GnomAD4 exome AF: 0.838 AC: 1222308 AN: 1459100 Hom.: 514088 Cov.: 43 AF XY: 0.840 AC XY: 609496 AN XY: 725852

African (AFR) AF: 0.655 AC: 21903 AN: 33426

American (AMR) AF: 0.765 AC: 34035 AN: 44496

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 20447 AN: 26102

East Asian (EAS) AF: 0.644 AC: 25540 AN: 39638

South Asian (SAS) AF: 0.874 AC: 75288 AN: 86120

European-Finnish (FIN) AF: 0.842 AC: 44906 AN: 53310

Middle Eastern (MID) AF: 0.797 AC: 4344 AN: 5452

European-Non Finnish (NFE) AF: 0.853 AC: 946617 AN: 1110314

Other (OTH) AF: 0.817 AC: 49228 AN: 60242

GnomAD4 genome AF: 0.779 AC: 118477 AN: 152020 Hom.: 46809 Cov.: 32 AF XY: 0.779 AC XY: 57851 AN XY: 74302

African (AFR) AF: 0.655 AC: 27142 AN: 41434

American (AMR) AF: 0.778 AC: 11893 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.782 AC: 2712 AN: 3470

East Asian (EAS) AF: 0.651 AC: 3343 AN: 5134

South Asian (SAS) AF: 0.878 AC: 4235 AN: 4824

European-Finnish (FIN) AF: 0.829 AC: 8773 AN: 10586

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.848 AC: 57627 AN: 67972

Other (OTH) AF: 0.802 AC: 1696 AN: 2114

Alfa AF: 0.805 Hom.: 27341

Bravo AF: 0.768

Asia WGS AF: 0.755 AC: 2626 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.88
DANN	Benign	0.43
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0040
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: rs437920; hg19: chr16-57937895; COSMIC: COSV51901195; COSMIC: COSV51901195;