Genetic Variant CNGA1:c.545+28delT (chr4-47942012-CA-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

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

Frequency

Genomes: 𝑓 0.78 ( 37387 hom., cov: 0)

Exomes 𝑓: 0.44 ( 3181 hom. )

Failed GnomAD Quality Control

Consequence

CNGA1
NM_001379270.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.500

Publications

3 publications found

Variant links:

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]

CNGA1 links:

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]

NIPAL1 links:

LOC101927157 (HGNC:):

LOC101927157 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 4-47942012-CA-C is Benign according to our data. Variant chr4-47942012-CA-C is described in ClinVar as Benign. ClinVar VariationId is 1235728.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGA1	NM_001379270.1	MANE Select	c.545+28delT	intron	N/A	NP_001366199.1	P29973
CNGA1	NM_000087.5		c.545+28delT	intron	N/A	NP_000078.3	P29973
CNGA1	NM_001142564.2		c.545+28delT	intron	N/A	NP_001136036.2	P29973

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CNGA1	ENST00000514170.7	TSL:5 MANE Select	c.545+28delT	intron	N/A	ENSP00000426862.3	P29973
CNGA1	ENST00000402813.9	TSL:1	c.545+28delT	intron	N/A	ENSP00000384264.5	P29973
CNGA1	ENST00000420489.7	TSL:2	c.545+28delT	intron	N/A	ENSP00000389881.3	P29973

Frequencies

GnomAD3 genomes

AF:

0.776

AC:

99136

AN:

127692

Hom.:

37397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.836

Gnomad AMI

AF:

0.789

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.954

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.773

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.732

Gnomad OTH

AF:

0.754

GnomAD2 exomes

AF:

0.437

AC:

60711

AN:

138906

AF XY:

0.434

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.416

Gnomad EAS exome

AF:

0.468

Gnomad FIN exome

AF:

0.431

Gnomad NFE exome

AF:

0.426

Gnomad OTH exome

AF:

0.436

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.443

AC:

457010

AN:

1031280

Hom.:

3181

Cov.:

AF XY:

0.443

AC XY:

232304

AN XY:

524808

show subpopulations

African (AFR)

AF:

0.463

AC:

10471

AN:

22598

American (AMR)

AF:

0.450

AC:

15113

AN:

33602

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

8744

AN:

21446

East Asian (EAS)

AF:

0.482

AC:

16126

AN:

33438

South Asian (SAS)

AF:

0.435

AC:

29065

AN:

66840

European-Finnish (FIN)

AF:

0.444

AC:

16956

AN:

38176

Middle Eastern (MID)

AF:

0.426

AC:

1630

AN:

3824

European-Non Finnish (NFE)

AF:

0.442

AC:

338853

AN:

766470

Other (OTH)

AF:

0.447

AC:

20052

AN:

44886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

15553

31107

46660

62214

77767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11622

23244

34866

46488

58110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.776

AC:

99132

AN:

127702

Hom.:

37387

Cov.:

AF XY:

0.778

AC XY:

47715

AN XY:

61308

show subpopulations

African (AFR)

AF:

0.835

AC:

28455

AN:

34062

American (AMR)

AF:

0.810

AC:

10302

AN:

12720

Ashkenazi Jewish (ASJ)

AF:

0.662

AC:

2024

AN:

3058

East Asian (EAS)

AF:

0.954

AC:

4242

AN:

4448

South Asian (SAS)

AF:

0.736

AC:

2911

AN:

3956

European-Finnish (FIN)

AF:

0.773

AC:

5519

AN:

7136

Middle Eastern (MID)

AF:

0.686

AC:

166

AN:

242

European-Non Finnish (NFE)

AF:

0.732

AC:

43593

AN:

59572

Other (OTH)

AF:

0.755

AC:

1295

AN:

1716

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

991

1983

2974

3966

4957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

734

1468

2202

2936

3670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.617

Hom.:

1208

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.50

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over