chrX-49215262-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001256789.3(CACNA1F):c.3439-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,207,806 control chromosomes in the GnomAD database, including 5 homozygotes. There are 1,084 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., 51 hem., cov: 22)

Exomes 𝑓: 0.0027 ( 5 hom. 1033 hem. )

Consequence

CACNA1F
NM_001256789.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.20

Publications

0 publications found

Variant links:

Genes affected

CACNA1F (HGNC:1393): (calcium voltage-gated channel subunit alpha1 F) This gene encodes a multipass transmembrane protein that functions as an alpha-1 subunit of the voltage-dependent calcium channel, which mediates the influx of calcium ions into the cell. The encoded protein forms a complex of alpha-1, alpha-2/delta, beta, and gamma subunits in a 1:1:1:1 ratio. Mutations in this gene can cause X-linked eye disorders, including congenital stationary night blindness type 2A, cone-rod dystropy, and Aland Island eye disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Aug 2013]

CACNA1F Gene-Disease associations (from GenCC):

Aland island eye disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
inherited retinal dystrophy
Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
congenital stationary night blindness 2A
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
X-linked cone-rod dystrophy 3
Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital stationary night blindness
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CACNA1F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant X-49215262-G-A is Benign according to our data. Variant chrX-49215262-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 445846.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00189 (209/110691) while in subpopulation SAS AF = 0.0043 (11/2560). AF 95% confidence interval is 0.00241. There are 0 homozygotes in GnomAd4. There are 51 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High AC in GnomAd4 at 209 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3 link	c.3439-18C>T		intron_variant	Intron 28 of 47	ENST00000323022.10	NP_001243718.1	O60840-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CACNA1F	ENST00000323022.10 link	c.3439-18C>T	intron_variant	Intron 28 of 47	1	NM_001256789.3	ENSP00000321618.6	O60840-2
CACNA1F	ENST00000376265.2 link	c.3472-18C>T	intron_variant	Intron 28 of 47	1		ENSP00000365441.2	O60840-1
CACNA1F	ENST00000376251.5 link	c.3277-18C>T	intron_variant	Intron 28 of 47	1		ENSP00000365427.1	O60840-4

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

210

AN:

110640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000792

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00172

Gnomad ASJ

AF:

0.00686

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00428

Gnomad FIN

AF:

0.000505

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00240

Gnomad OTH

AF:

0.00405

GnomAD2 exomes

AF:

0.00278

AC:

504

AN:

181566

AF XY:

0.00314

show subpopulations

Gnomad AFR exome

AF:

0.000537

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.00590

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000382

Gnomad NFE exome

AF:

0.00272

Gnomad OTH exome

AF:

0.00400

GnomAD4 exome

AF:

0.00268

AC:

2937

AN:

1097115

Hom.:

Cov.:

AF XY:

0.00285

AC XY:

1033

AN XY:

362507

show subpopulations

African (AFR)

AF:

0.000568

AC:

AN:

26389

American (AMR)

AF:

0.00267

AC:

AN:

35144

Ashkenazi Jewish (ASJ)

AF:

0.00511

AC:

AN:

19377

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.00702

AC:

379

AN:

54021

European-Finnish (FIN)

AF:

0.000247

AC:

AN:

40465

Middle Eastern (MID)

AF:

0.0104

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00254

AC:

2138

AN:

841328

Other (OTH)

AF:

0.00345

AC:

159

AN:

46059

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

108

215

323

430

538

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

168

252

336

420

<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:

0.00189

AC:

209

AN:

110691

Hom.:

Cov.:

AF XY:

0.00155

AC XY:

AN XY:

32897

show subpopulations

African (AFR)

AF:

0.000790

AC:

AN:

30388

American (AMR)

AF:

0.00172

AC:

AN:

10460

Ashkenazi Jewish (ASJ)

AF:

0.00686

AC:

AN:

2624

East Asian (EAS)

AF:

0.00

AC:

AN:

3500

South Asian (SAS)

AF:

0.00430

AC:

AN:

2560

European-Finnish (FIN)

AF:

0.000505

AC:

AN:

5937

Middle Eastern (MID)

AF:

0.00926

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00240

AC:

127

AN:

52825

Other (OTH)

AF:

0.00400

AC:

AN:

1500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00232

Hom.:

Bravo

AF:

0.00197

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 15, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 19, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aland island eye disease

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital stationary night blindness 2A

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

X-linked cone-rod dystrophy 3

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.7

(source)

DANN

Benign

0.62

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over