4-47943438-C-G

Variant names:

• chr4-47943438-C-G
• rs6819506
• NM_001379270.1:c.288-26G>C

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.288-26G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,326,930 control chromosomes in the GnomAD database, including 435,457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.83 (52558 hom., cov: 29)
  • Exomes 𝑓: 0.81 (382899 hom.)
• Consequence: CNGA1 NM_001379270.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.157
• Publications: 9 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 4-47943438-C-G is Benign according to our data. Variant chr4-47943438-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278730.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNGA1	NM_001379270.1	MANE Select	c.288-26G>C		intron	N/A	NP_001366199.1	P29973
	CNGA1	NM_000087.5		c.288-26G>C		intron	N/A	NP_000078.3	P29973
	CNGA1	NM_001142564.2		c.288-26G>C		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.288-26G>C		intron	N/A	ENSP00000426862.3	P29973
	CNGA1	ENST00000402813.9	TSL:1	c.288-26G>C		intron	N/A	ENSP00000384264.5	P29973
	CNGA1	ENST00000420489.7	TSL:2	c.288-26G>C		intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126001 AN: 151670 Hom.: 52516 Cov.: 29

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.695

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.803

Gnomad OTH AF: 0.808

GnomAD2 exomes AF: 0.826 AC: 95715 AN: 115822 AF XY: 0.820

Gnomad AFR exome AF: 0.848

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.686

Gnomad EAS exome AF: 0.974

Gnomad FIN exome AF: 0.875

Gnomad NFE exome AF: 0.797

Gnomad OTH exome AF: 0.803

GnomAD4 exome AF: 0.806 AC: 947050 AN: 1175142 Hom.: 382899 Cov.: 17 AF XY: 0.805 AC XY: 472782 AN XY: 587542

African (AFR) AF: 0.848 AC: 21310 AN: 25134

American (AMR) AF: 0.883 AC: 19664 AN: 22260

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 15092 AN: 22030

East Asian (EAS) AF: 0.972 AC: 33234 AN: 34178

South Asian (SAS) AF: 0.788 AC: 52296 AN: 66396

European-Finnish (FIN) AF: 0.875 AC: 41935 AN: 47926

Middle Eastern (MID) AF: 0.695 AC: 2622 AN: 3770

European-Non Finnish (NFE) AF: 0.798 AC: 720845 AN: 903622

Other (OTH) AF: 0.804 AC: 40052 AN: 49826

GnomAD4 genome AF: 0.831 AC: 126102 AN: 151788 Hom.: 52558 Cov.: 29 AF XY: 0.833 AC XY: 61784 AN XY: 74156

African (AFR) AF: 0.851 AC: 35208 AN: 41382

American (AMR) AF: 0.863 AC: 13159 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 2410 AN: 3468

East Asian (EAS) AF: 0.979 AC: 5070 AN: 5180

South Asian (SAS) AF: 0.793 AC: 3806 AN: 4800

European-Finnish (FIN) AF: 0.881 AC: 9222 AN: 10472

Middle Eastern (MID) AF: 0.753 AC: 220 AN: 292

European-Non Finnish (NFE) AF: 0.803 AC: 54551 AN: 67946

Other (OTH) AF: 0.811 AC: 1702 AN: 2098

Alfa AF: 0.793 Hom.: 8486

Bravo AF: 0.831

Asia WGS AF: 0.887 AC: 3083 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.5
DANN	Benign	0.55
PhyloP100		0.16
BranchPoint Hunter		3.0
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: rs6819506; hg19: chr4-47945455;