4-47942012-CAAAAA-C

Position:

• chr4-47942012-CAAAAA-C

Variant summary

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

The NM_001379270.1(CNGA1):​c.545+24_545+28delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000052 in 1,037,932 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000052 (0 hom.)
  • Failed GnomAD Quality Control
• 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:):

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+24_545+28delTTTTT		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+24_545+28delTTTTT		intron_variant		5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 127604 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00

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: 0.0000520 AC: 54 AN: 1037932 Hom.: 0 AF XY: 0.0000473 AC XY: 25 AN XY: 528486

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000592

Gnomad4 ASJ exome AF: 0.0000460

Gnomad4 EAS exome AF: 0.0000299

Gnomad4 SAS exome AF: 0.0000296

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000597

Gnomad4 OTH exome AF: 0.0000442

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 127604 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 61218

Gnomad4 AFR AF: 0.00

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

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;