4-47942012-CAAAAAA-CAA

Variant names:

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

Variant summary

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

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
• 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+25_545+28delTTTT		intron	N/A	NP_001366199.1	P29973
	CNGA1	NM_000087.5		c.545+25_545+28delTTTT		intron	N/A	NP_000078.3	P29973
	CNGA1	NM_001142564.2		c.545+25_545+28delTTTT		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+25_545+28delTTTT		intron	N/A	ENSP00000426862.3	P29973
	CNGA1	ENST00000402813.9	TSL:1	c.545+25_545+28delTTTT		intron	N/A	ENSP00000384264.5	P29973
	CNGA1	ENST00000420489.7	TSL:2	c.545+25_545+28delTTTT		intron	N/A	ENSP00000389881.3	P29973

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

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

African (AFR) AF: 0.000397 AC: 9 AN: 22664

American (AMR) AF: 0.000356 AC: 12 AN: 33752

Ashkenazi Jewish (ASJ) AF: 0.000138 AC: 3 AN: 21726

East Asian (EAS) AF: 0.0000897 AC: 3 AN: 33458

South Asian (SAS) AF: 0.000207 AC: 14 AN: 67614

European-Finnish (FIN) AF: 0.000286 AC: 11 AN: 38402

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

European-Non Finnish (NFE) AF: 0.000426 AC: 328 AN: 770314

Other (OTH) AF: 0.000398 AC: 18 AN: 45174

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

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

African (AFR) AF: 0.0000294 AC: 1 AN: 34002

American (AMR) AF: 0.00 AC: 0 AN: 12670

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: 7092

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 59566

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.0

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

Other links and lift over

dbSNP: rs10709670; hg19: chr4-47944029;