4-47942012-CAAA-C

Position:

• chr4-47942012-CAAA-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001379270.1(CNGA1):​c.545+26_545+28delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,159,706 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (0 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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: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]

LOC101927157 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA1	NM_001379270.1	c.545+26_545+28delTTT		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+26_545+28delTTT		intron_variant		5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes AF: 0.000125 AC: 16 AN: 127588 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000294

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000705

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.000588

GnomAD4 exome AF: 0.00433 AC: 4473 AN: 1032116 Hom.: 0 AF XY: 0.00408 AC XY: 2143 AN XY: 525650

Gnomad4 AFR exome AF: 0.00443

Gnomad4 AMR exome AF: 0.00589

Gnomad4 ASJ exome AF: 0.00166

Gnomad4 EAS exome AF: 0.00216

Gnomad4 SAS exome AF: 0.00267

Gnomad4 FIN exome AF: 0.00393

Gnomad4 NFE exome AF: 0.00463

Gnomad4 OTH exome AF: 0.00396

GnomAD4 genome AF: 0.000125 AC: 16 AN: 127590 Hom.: 0 Cov.: 0 AF XY: 0.0000490 AC XY: 3 AN XY: 61232

Gnomad4 AFR AF: 0.0000294

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000705

Gnomad4 NFE AF: 0.000151

Gnomad4 OTH AF: 0.000585

ClinVar

Not reported in ClinVar

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;