rs59800634

Positions:

• chr4-47942012-C-CA
• chr4-47942012-CAAAAA-C
• chr4-47942012-CAA-C
• chr4-47942012-CAAAAAA-C
• chr4-47942012-C-CAA
• chr4-47942012-CA-C
• chr4-47942012-CAAAA-C
• chr4-47942012-C-CAAA
• chr4-47942012-CAAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001379270.1(CNGA1):​c.545+28dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (16 hom., cov: 0)
  • Exomes 𝑓: 0.041 (1 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500

Genes affected

CNGA1 (HGNC:2148): (cyclic nucleotide gated channel subunit alpha 1) The protein encoded by this gene is involved in phototransduction. Along with another protein, the encoded protein forms a cGMP-gated cation channel in the plasma membrane, allowing depolarization of rod photoreceptors. This represents the last step in the phototransduction pathway. Defects in this gene are a cause of retinitis pigmentosa autosomal recessive (ARRP) disease. Multiple transcript variants have been found for this gene. [provided by RefSeq, Oct 2019]

NIPAL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-47942012-C-CA is Benign according to our data. Variant chr4-47942012-C-CA is described in ClinVar as [Likely_benign]. Clinvar id is 1706785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (1919/127572) while in subpopulation AFR AF= 0.0251 (853/34046). AF 95% confidence interval is 0.0237. There are 16 homozygotes in gnomad4. There are 909 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA1	NM_001379270.1	c.545+28dupT		intron_variant		ENST00000514170.7	NP_001366199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNGA1	ENST00000514170.7	c.545+28dupT		intron_variant		5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 1917 AN: 127568 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.00742

Gnomad ASJ AF: 0.00589

Gnomad EAS AF: 0.000448

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.00902

Gnomad MID AF: 0.00752

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00765

GnomAD4 exome AF: 0.0406 AC: 41329 AN: 1018862 Hom.: 1 Cov.: 0 AF XY: 0.0405 AC XY: 20991 AN XY: 518340

Gnomad4 AFR exome AF: 0.0362

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0703

Gnomad4 EAS exome AF: 0.0105

Gnomad4 SAS exome AF: 0.0494

Gnomad4 FIN exome AF: 0.0256

Gnomad4 NFE exome AF: 0.0417

Gnomad4 OTH exome AF: 0.0407

GnomAD4 genome AF: 0.0150 AC: 1919 AN: 127572 Hom.: 16 Cov.: 0 AF XY: 0.0148 AC XY: 909 AN XY: 61220

Gnomad4 AFR AF: 0.0251

Gnomad4 AMR AF: 0.00741

Gnomad4 ASJ AF: 0.00589

Gnomad4 EAS AF: 0.000450

Gnomad4 SAS AF: 0.0217

Gnomad4 FIN AF: 0.00902

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00761

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10709670; hg19: chr4-47944029;