4-47942012-C-CAA

Position:

• chr4-47942012-C-CAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001379270.1(CNGA1):​c.545+27_545+28dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (0 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.500

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00426 (4396/1032466) while in subpopulation SAS AF= 0.00651 (436/66950). AF 95% confidence interval is 0.00601. There are 0 homozygotes in gnomad4_exome. There are 2240 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CNGA1	NM_001379270.1	c.545+27_545+28dupTT		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+28_545+29insTT		intron_variant		5	NM_001379270.1	ENSP00000426862.3

Frequencies

GnomAD3 genomes AF: 0.000212 AC: 27 AN: 127588 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000324

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000789

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000141

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00426 AC: 4396 AN: 1032466 Hom.: 0 Cov.: 0 AF XY: 0.00426 AC XY: 2240 AN XY: 525620

Gnomad4 AFR exome AF: 0.00496

Gnomad4 AMR exome AF: 0.00247

Gnomad4 ASJ exome AF: 0.00758

Gnomad4 EAS exome AF: 0.000479

Gnomad4 SAS exome AF: 0.00651

Gnomad4 FIN exome AF: 0.00240

Gnomad4 NFE exome AF: 0.00430

Gnomad4 OTH exome AF: 0.00400

GnomAD4 genome AF: 0.000212 AC: 27 AN: 127588 Hom.: 0 Cov.: 0 AF XY: 0.000261 AC XY: 16 AN XY: 61214

Gnomad4 AFR AF: 0.000324

Gnomad4 AMR AF: 0.0000789

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000141

Gnomad4 NFE AF: 0.000235

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;