chr16-57882799-C-CTT

Variant names:

• chr16-57882799-C-CTT
• rs71155213
• NM_001297.5:c.*1363_*1364dupAA

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001297.5(CNGB1):​c.*1363_*1364dupAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.022 (58 hom., cov: 18)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNGB1 NM_001297.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.00
• Publications: 0 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: Likely_benign. The variant received -5 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0216 (2936/136064) while in subpopulation AFR AF = 0.0451 (1658/36770). AF 95% confidence interval is 0.0433. There are 58 homozygotes in GnomAd4. There are 1337 alleles in the male GnomAd4 subpopulation. Median coverage is 18. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 58 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.*1363_*1364dupAA		3_prime_UTR	Exon 33 of 33	NP_001288.3	Q14028-1
	CNGB1	NM_001286130.2		c.*1363_*1364dupAA		3_prime_UTR	Exon 33 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.*1363_*1364dupAA		3_prime_UTR	Exon 33 of 33	ENSP00000251102.8	Q14028-1

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 2943 AN: 136046 Hom.: 58 Cov.: 18

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.0198

Gnomad EAS AF: 0.000209

Gnomad SAS AF: 0.00232

Gnomad FIN AF: 0.00719

Gnomad MID AF: 0.0479

Gnomad NFE AF: 0.0153

Gnomad OTH AF: 0.0210

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0216 AC: 2936 AN: 136064 Hom.: 58 Cov.: 18 AF XY: 0.0204 AC XY: 1337 AN XY: 65588

African (AFR) AF: 0.0451 AC: 1658 AN: 36770

American (AMR) AF: 0.0102 AC: 138 AN: 13518

Ashkenazi Jewish (ASJ) AF: 0.0198 AC: 64 AN: 3228

East Asian (EAS) AF: 0.000210 AC: 1 AN: 4766

South Asian (SAS) AF: 0.00187 AC: 8 AN: 4288

European-Finnish (FIN) AF: 0.00719 AC: 54 AN: 7514

Middle Eastern (MID) AF: 0.0414 AC: 11 AN: 266

European-Non Finnish (NFE) AF: 0.0153 AC: 962 AN: 62946

Other (OTH) AF: 0.0209 AC: 40 AN: 1918

Alfa AF: 0.00308 Hom.: 199

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Retinitis Pigmentosa, Recessive (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71155213; hg19: chr16-57916703;