rs3991715

Variant names:

• chr16-57917490-T-G
• rs3991715
• NM_001297.5:c.1958-14A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-57917490-T-G
• chr16-57917490-T-A

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.1958-14A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,612,868 control chromosomes in the GnomAD database, including 58,880 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7595 hom., cov: 31)
  • Exomes 𝑓: 0.26 (51285 hom.)
• Consequence: CNGB1 NM_001297.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.25
• Publications: 6 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=-0.84).
• BP6: Variant 16-57917490-T-G is Benign according to our data. Variant chr16-57917490-T-G is described in ClinVar as Benign. ClinVar VariationId is 257960.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 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.1958-14A>C		intron	N/A	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.1940-14A>C		intron	N/A	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.1958-14A>C		intron	N/A	ENSP00000251102.8	Q14028-1
	CNGB1	ENST00000564448.5	TSL:1	c.1940-14A>C		intron	N/A	ENSP00000454633.1	Q14028-4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46141 AN: 151748 Hom.: 7580 Cov.: 31

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.271 AC: 67551 AN: 248924 AF XY: 0.274

Gnomad AFR exome AF: 0.435

Gnomad AMR exome AF: 0.244

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.175

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.254

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.261 AC: 380651 AN: 1461000 Hom.: 51285 Cov.: 35 AF XY: 0.263 AC XY: 190952 AN XY: 726866

African (AFR) AF: 0.440 AC: 14732 AN: 33460

American (AMR) AF: 0.244 AC: 10925 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 7468 AN: 26136

East Asian (EAS) AF: 0.179 AC: 7106 AN: 39692

South Asian (SAS) AF: 0.332 AC: 28623 AN: 86214

European-Finnish (FIN) AF: 0.267 AC: 14241 AN: 53412

Middle Eastern (MID) AF: 0.392 AC: 2140 AN: 5460

European-Non Finnish (NFE) AF: 0.251 AC: 278797 AN: 1111568

Other (OTH) AF: 0.275 AC: 16619 AN: 60336

GnomAD4 genome AF: 0.304 AC: 46199 AN: 151868 Hom.: 7595 Cov.: 31 AF XY: 0.304 AC XY: 22562 AN XY: 74232

African (AFR) AF: 0.435 AC: 17984 AN: 41374

American (AMR) AF: 0.245 AC: 3738 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 970 AN: 3468

East Asian (EAS) AF: 0.172 AC: 888 AN: 5164

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4810

European-Finnish (FIN) AF: 0.269 AC: 2840 AN: 10550

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17269 AN: 67934

Other (OTH) AF: 0.281 AC: 592 AN: 2104

Alfa AF: 0.293 Hom.: 2676

Bravo AF: 0.306

Asia WGS AF: 0.283 AC: 988 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.094
DANN	Benign	0.36
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3991715; hg19: chr16-57951394; COSMIC: COSV51897783;