4-47942012-CAAAAAA-CA

Variant names:

• chr4-47942012-CAAAAA-C
• rs10709670
• NM_001379270.1:c.545+24_545+28delTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

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
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379270.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA1	NM_001379270.1	MANE Select	c.545+24_545+28delTTTTT		intron	N/A	NP_001366199.1	P29973
	CNGA1	NM_000087.5		c.545+24_545+28delTTTTT		intron	N/A	NP_000078.3	P29973
	CNGA1	NM_001142564.2		c.545+24_545+28delTTTTT		intron	N/A	NP_001136036.2	P29973

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA1	ENST00000514170.7	TSL:5 MANE Select	c.545+24_545+28delTTTTT		intron	N/A	ENSP00000426862.3	P29973
	CNGA1	ENST00000402813.9	TSL:1	c.545+24_545+28delTTTTT		intron	N/A	ENSP00000384264.5	P29973
	CNGA1	ENST00000420489.7	TSL:2	c.545+24_545+28delTTTTT		intron	N/A	ENSP00000389881.3	P29973

Frequencies

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

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22676

American (AMR) AF: 0.0000592 AC: 2 AN: 33780

Ashkenazi Jewish (ASJ) AF: 0.0000460 AC: 1 AN: 21734

East Asian (EAS) AF: 0.0000299 AC: 1 AN: 33492

South Asian (SAS) AF: 0.0000296 AC: 2 AN: 67666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3870

European-Non Finnish (NFE) AF: 0.0000597 AC: 46 AN: 771048

Other (OTH) AF: 0.0000442 AC: 2 AN: 45216

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00 AC: 0 AN: 34002

American (AMR) AF: 0.00 AC: 0 AN: 12672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3058

East Asian (EAS) AF: 0.00 AC: 0 AN: 4462

South Asian (SAS) AF: 0.00 AC: 0 AN: 3984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7096

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59570

Other (OTH) AF: 0.00 AC: 0 AN: 1702

Alfa AF: 0.00 Hom.: 1208

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10709670; hg19: chr4-47944029;