rs1972883

Variant names:

• chr4-47949928-G-A
• rs1972883
• NM_001379270.1:c.225-33C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-47949928-G-A
• chr4-47949928-G-C
• chr4-47949928-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379270.1(CNGA1):​c.225-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 1,604,472 control chromosomes in the GnomAD database, including 536,713 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55480 hom., cov: 33)
  • Exomes 𝑓: 0.81 (481233 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.142
• Publications: 15 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 4-47949928-G-A is Benign according to our data. Variant chr4-47949928-G-A is described in ClinVar as Benign. ClinVar VariationId is 1217359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA1	NM_001379270.1	MANE Select	c.225-33C>T		intron	N/A	NP_001366199.1
	CNGA1	NM_000087.5		c.225-33C>T		intron	N/A	NP_000078.3
	CNGA1	NM_001142564.2		c.225-33C>T		intron	N/A	NP_001136036.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA1	ENST00000514170.7	TSL:5 MANE Select	c.225-33C>T		intron	N/A	ENSP00000426862.3
	CNGA1	ENST00000402813.9	TSL:1	c.225-33C>T		intron	N/A	ENSP00000384264.5
	CNGA1	ENST00000420489.7	TSL:2	c.225-33C>T		intron	N/A	ENSP00000389881.3

Frequencies

GnomAD3 genomes AF: 0.851 AC: 129435 AN: 152128 Hom.: 55422 Cov.: 33

Gnomad AFR AF: 0.920

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.880

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.826

GnomAD2 exomes AF: 0.837 AC: 207969 AN: 248476 AF XY: 0.827

Gnomad AFR exome AF: 0.925

Gnomad AMR exome AF: 0.909

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.974

Gnomad FIN exome AF: 0.873

Gnomad NFE exome AF: 0.801

Gnomad OTH exome AF: 0.815

GnomAD4 exome AF: 0.813 AC: 1180078 AN: 1452226 Hom.: 481233 Cov.: 29 AF XY: 0.810 AC XY: 586017 AN XY: 723136

African (AFR) AF: 0.924 AC: 30770 AN: 33318

American (AMR) AF: 0.902 AC: 40312 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 17913 AN: 26034

East Asian (EAS) AF: 0.973 AC: 38546 AN: 39632

South Asian (SAS) AF: 0.790 AC: 67950 AN: 85990

European-Finnish (FIN) AF: 0.874 AC: 46666 AN: 53384

Middle Eastern (MID) AF: 0.719 AC: 4125 AN: 5740

European-Non Finnish (NFE) AF: 0.802 AC: 885023 AN: 1103360

Other (OTH) AF: 0.812 AC: 48773 AN: 60088

GnomAD4 genome AF: 0.851 AC: 129554 AN: 152246 Hom.: 55480 Cov.: 33 AF XY: 0.852 AC XY: 63439 AN XY: 74442

African (AFR) AF: 0.921 AC: 38248 AN: 41550

American (AMR) AF: 0.871 AC: 13322 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2409 AN: 3470

East Asian (EAS) AF: 0.979 AC: 5074 AN: 5184

South Asian (SAS) AF: 0.793 AC: 3828 AN: 4826

European-Finnish (FIN) AF: 0.880 AC: 9329 AN: 10602

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.803 AC: 54617 AN: 68000

Other (OTH) AF: 0.829 AC: 1752 AN: 2114

Alfa AF: 0.820 Hom.: 13104

Bravo AF: 0.854

Asia WGS AF: 0.893 AC: 3106 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Retinitis pigmentosa 49 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.22
PhyloP100		0.14
Mutation Taster		=100/0	polymorphism (auto)

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: rs1972883; hg19: chr4-47951945;