4-47942012-CAA-C

Position:

• chr4-47942012-CAA-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001379270.1(CNGA1):​c.545+27_545+28del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 1,150,820 control chromosomes in the GnomAD database, including 133 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (80 hom., cov: 0)
  • Exomes 𝑓: 0.083 (53 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.526

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]

LOC101927157 (HGNC:):

NIPAL1 (HGNC:27194): (NIPA like domain containing 1) Predicted to enable magnesium ion transmembrane transporter activity. Predicted to be involved in magnesium ion transport. Predicted to be integral component of membrane. Predicted to be active in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-47942012-CAA-C is Benign according to our data. Variant chr4-47942012-CAA-C is described in ClinVar as [Benign]. Clinvar id is 1226008.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.087 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGA1	NM_001379270.1	c.545+27_545+28del		intron_variant		ENST00000514170.7
LOC101927157	NR_125879.1	n.479-16995_479-16994del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGA1	ENST00000514170.7	c.545+27_545+28del		intron_variant		5	NM_001379270.1	P1

Frequencies

GnomAD3 genomes AF: 0.0367 AC: 4687 AN: 127614 Hom.: 80 Cov.: 0

Gnomad AFR AF: 0.0198

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0271

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00426

Gnomad SAS AF: 0.0226

Gnomad FIN AF: 0.0600

Gnomad MID AF: 0.0455

Gnomad NFE AF: 0.0500

Gnomad OTH AF: 0.0411

GnomAD4 exome AF: 0.0830 AC: 84892 AN: 1023200 Hom.: 53 AF XY: 0.0815 AC XY: 42469 AN XY: 520794

Gnomad4 AFR exome AF: 0.0701

Gnomad4 AMR exome AF: 0.0859

Gnomad4 ASJ exome AF: 0.0523

Gnomad4 EAS exome AF: 0.0599

Gnomad4 SAS exome AF: 0.0539

Gnomad4 FIN exome AF: 0.0939

Gnomad4 NFE exome AF: 0.0875

Gnomad4 OTH exome AF: 0.0753

GnomAD4 genome AF: 0.0368 AC: 4691 AN: 127620 Hom.: 80 Cov.: 0 AF XY: 0.0353 AC XY: 2165 AN XY: 61248

Gnomad4 AFR AF: 0.0199

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00428

Gnomad4 SAS AF: 0.0225

Gnomad4 FIN AF: 0.0600

Gnomad4 NFE AF: 0.0500

Gnomad4 OTH AF: 0.0415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

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;