NM_001379270.1:c.2049C>T

Variant names:

• chr4-47936433-G-A
• rs369407883
• NM_001379270.1:c.2049C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001379270.1(CNGA1):​c.2049C>T​(p.Ile683Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000496 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I683I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CNGA1 NM_001379270.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.439
• Publications: 0 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 4-47936433-G-A is Benign according to our data. Variant chr4-47936433-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 796646.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.439 with no splicing effect.

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.2049C>T	p.Ile683Ile	synonymous	Exon 11 of 11	NP_001366199.1	P29973
	CNGA1	NM_000087.5		c.2049C>T	p.Ile683Ile	synonymous	Exon 11 of 11	NP_000078.3	P29973
	CNGA1	NM_001142564.2		c.2049C>T	p.Ile683Ile	synonymous	Exon 10 of 10	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.2049C>T	p.Ile683Ile	synonymous	Exon 11 of 11	ENSP00000426862.3	P29973
	CNGA1	ENST00000402813.9	TSL:1	c.2049C>T	p.Ile683Ile	synonymous	Exon 10 of 10	ENSP00000384264.5	P29973
	CNGA1	ENST00000420489.7	TSL:2	c.2049C>T	p.Ile683Ile	synonymous	Exon 11 of 11	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32

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: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248908 AF XY: 0.0000222

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461838 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.000134 AC: 6 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

Other (OTH) AF: 0.0000166 AC: 1 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74320

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.81
PhyloP100		-0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs369407883; hg19: chr4-47938450;