4-47942012-CAAAAAA-CAAAAAAA

Variant names:

• chr4-47942012-C-CA
• rs10709670
• NM_001379270.1:c.545+28dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001379270.1(CNGA1):​c.545+28dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (16 hom., cov: 0)
  • Exomes 𝑓: 0.041 (1 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.500
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 4-47942012-C-CA is Benign according to our data. Variant chr4-47942012-C-CA is described in ClinVar as Likely_benign. ClinVar VariationId is 1706785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.015 (1919/127572) while in subpopulation AFR AF = 0.0251 (853/34046). AF 95% confidence interval is 0.0237. There are 16 homozygotes in GnomAd4. There are 909 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 16 AD,AR gene

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+28dupT		intron	N/A	NP_001366199.1	P29973
	CNGA1	NM_000087.5		c.545+28dupT		intron	N/A	NP_000078.3	P29973
	CNGA1	NM_001142564.2		c.545+28dupT		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+28_545+29insT		intron	N/A	ENSP00000426862.3	P29973
	CNGA1	ENST00000402813.9	TSL:1	c.545+28_545+29insT		intron	N/A	ENSP00000384264.5	P29973
	CNGA1	ENST00000420489.7	TSL:2	c.545+28_545+29insT		intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 1917 AN: 127568 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.0189

Gnomad AMR AF: 0.00742

Gnomad ASJ AF: 0.00589

Gnomad EAS AF: 0.000448

Gnomad SAS AF: 0.0218

Gnomad FIN AF: 0.00902

Gnomad MID AF: 0.00752

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00765

GnomAD2 exomes AF: 0.0439 AC: 6097 AN: 138906 AF XY: 0.0472

Gnomad AFR exome AF: 0.0335

Gnomad AMR exome AF: 0.0289

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.0169

Gnomad FIN exome AF: 0.0262

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0480

GnomAD4 exome AF: 0.0406 AC: 41329 AN: 1018862 Hom.: 1 Cov.: 0 AF XY: 0.0405 AC XY: 20991 AN XY: 518340

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

African (AFR) AF: 0.0362 AC: 806 AN: 22240

American (AMR) AF: 0.0248 AC: 821 AN: 33050

Ashkenazi Jewish (ASJ) AF: 0.0703 AC: 1482 AN: 21080

East Asian (EAS) AF: 0.0105 AC: 345 AN: 32832

South Asian (SAS) AF: 0.0494 AC: 3236 AN: 65456

European-Finnish (FIN) AF: 0.0256 AC: 965 AN: 37722

Middle Eastern (MID) AF: 0.0556 AC: 211 AN: 3794

European-Non Finnish (NFE) AF: 0.0417 AC: 31658 AN: 758338

Other (OTH) AF: 0.0407 AC: 1805 AN: 44350

⚠️ 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: 0.0150 AC: 1919 AN: 127572 Hom.: 16 Cov.: 0 AF XY: 0.0148 AC XY: 909 AN XY: 61220

African (AFR) AF: 0.0251 AC: 853 AN: 34046

American (AMR) AF: 0.00741 AC: 94 AN: 12680

Ashkenazi Jewish (ASJ) AF: 0.00589 AC: 18 AN: 3056

East Asian (EAS) AF: 0.000450 AC: 2 AN: 4444

South Asian (SAS) AF: 0.0217 AC: 86 AN: 3964

European-Finnish (FIN) AF: 0.00902 AC: 64 AN: 7098

Middle Eastern (MID) AF: 0.00826 AC: 2 AN: 242

European-Non Finnish (NFE) AF: 0.0130 AC: 772 AN: 59542

Other (OTH) AF: 0.00761 AC: 13 AN: 1708

Alfa AF: 0.0298 Hom.: 1208

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;