4-47943438-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379270.1(CNGA1):c.288-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,326,930 control chromosomes in the GnomAD database, including 435,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.83 (52558 hom., cov: 29)
  • Exomes 𝑓: 0.81 (382899 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.157

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-47943438-C-G is Benign according to our data. Variant chr4-47943438-C-G is described in ClinVar as [Benign]. Clinvar id is 1278730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNGA1	NM_001379270.1	c.288-26G>C		intron_variant		ENST00000514170.7
LOC101927157	NR_125879.1	n.479-15586C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNGA1	ENST00000514170.7	c.288-26G>C		intron_variant		5	NM_001379270.1	P1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126001 AN: 151670 Hom.: 52516 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.808

GnomAD3 exomes AF: 0.826 AC: 95715 AN: 115822 Hom.: 39834 AF XY: 0.820 AC XY: 50852 AN XY: 62008

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.974

Gnomad SAS exome AF: 0.788

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.803

GnomAD4 exome AF: 0.806 AC: 947050 AN: 1175142 Hom.: 382899 Cov.: 17 AF XY: 0.805 AC XY: 472782 AN XY: 587542

Gnomad4 AFR exome AF: 0.848

Gnomad4 AMR exome AF: 0.883

Gnomad4 ASJ exome AF: 0.685

Gnomad4 EAS exome AF: 0.972

Gnomad4 SAS exome AF: 0.788

Gnomad4 FIN exome AF: 0.875

Gnomad4 NFE exome AF: 0.798

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.831 AC: 126102 AN: 151788 Hom.: 52558 Cov.: 29 AF XY: 0.833 AC XY: 61784 AN XY: 74156

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.695

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.881

Gnomad4 NFE AF: 0.803

Gnomad4 OTH AF: 0.811

Alfa AF: 0.793 Hom.: 8486

Bravo AF: 0.831

Asia WGS AF: 0.887 AC: 3083 AN: 3476

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

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	8.5
Dann	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6819506; hg19: chr4-47945455;