4-47942012-CAAAA-C

Variant names:

• chr4-47942012-CAAAA-C
• rs10709670
• NM_001379270.1:c.545+25_545+28delTTTT

Variant summary

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

The NM_001379270.1(CNGA1):​c.545+25_545+28delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,164,568 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 0.0000078 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00038 (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 rank	MANE	Protein	UniProt
CNGA1	NM_001379270.1	c.545+25_545+28delTTTT		intron_variant	Intron 9 of 10	ENST00000514170.7	NP_001366199.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNGA1	ENST00000514170.7	c.545+25_545+28delTTTT		intron_variant	Intron 9 of 10	5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes AF: 0.00000784 AC: 1 AN: 127594 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: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000384 AC: 398 AN: 1036974 Hom.: 0 AF XY: 0.000371 AC XY: 196 AN XY: 528034

Gnomad4 AFR exome AF: 0.000397

Gnomad4 AMR exome AF: 0.000356

Gnomad4 ASJ exome AF: 0.000138

Gnomad4 EAS exome AF: 0.0000897

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.000286

Gnomad4 NFE exome AF: 0.000426

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.00000784 AC: 1 AN: 127594 Hom.: 0 Cov.: 0 AF XY: 0.0000163 AC XY: 1 AN XY: 61212

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: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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;