16-57882799-C-CTT

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_001297.5(CNGB1):c.*1364_*1365insAA 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 18. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGB1	NM_001297.5	c.*1364_*1365insAA		3_prime_UTR_variant	33/33	ENST00000251102.13
CNGB1	NM_001286130.2	c.*1364_*1365insAA		3_prime_UTR_variant	33/33

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGB1	ENST00000251102.13	c.*1364_*1365insAA		3_prime_UTR_variant	33/33	1	NM_001297.5	P4

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

Gnomad4 NFE exome AF: 0.00

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

Gnomad4 AFR AF: 0.0451

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.0198

Gnomad4 EAS AF: 0.000210

Gnomad4 SAS AF: 0.00187

Gnomad4 FIN AF: 0.00719

Gnomad4 NFE AF: 0.0153

Gnomad4 OTH AF: 0.0209

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Retinitis Pigmentosa, Recessive Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71155213; hg19: chr16-57916703;