X-49219318-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256789.3(CACNA1F):c.2673+3G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 1,205,572 control chromosomes in the GnomAD database, including 1,438 homozygotes. There are 21,173 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 84 hom., 1330 hem., cov: 22)

Exomes 𝑓: 0.057 ( 1354 hom. 19843 hem. )

Consequence

CACNA1F
NM_001256789.3 splice_region, intron

Scores

Splicing: ADA: 0.0002534

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.999

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant X-49219318-C-T is Benign according to our data. Variant chrX-49219318-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 166778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3 link	c.2673+3G>A		splice_region_variant, intron_variant	Intron 21 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.2673+3G>A	splice_region_variant, intron_variant	Intron 21 of 47	1	NM_001256789.3	ENSP00000321618.6	O60840-2
CACNA1F	ENST00000376265.2 link	c.2706+3G>A	splice_region_variant, intron_variant	Intron 21 of 47	1		ENSP00000365441.2	O60840-1
CACNA1F	ENST00000376251.5 link	c.2511+3G>A	splice_region_variant, intron_variant	Intron 21 of 47	1		ENSP00000365427.1	O60840-4

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

4516

AN:

111126

Hom.:

Cov.:

AF XY:

0.0399

AC XY:

1328

AN XY:

33312

show subpopulations

Gnomad AFR

AF:

0.00910

Gnomad AMI

AF:

0.0849

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0638

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0212

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.0378

Gnomad NFE

AF:

0.0595

Gnomad OTH

AF:

0.0430

GnomAD3 exomes

AF:

0.0431

AC:

7500

AN:

174086

Hom.:

150

AF XY:

0.0416

AC XY:

2487

AN XY:

59784

show subpopulations

Gnomad AFR exome

AF:

0.00741

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.0623

Gnomad EAS exome

AF:

0.0000740

Gnomad SAS exome

AF:

0.0190

Gnomad FIN exome

AF:

0.0857

Gnomad NFE exome

AF:

0.0618

Gnomad OTH exome

AF:

0.0429

GnomAD4 exome

AF:

0.0567

AC:

62073

AN:

1094392

Hom.:

1354

Cov.:

AF XY:

0.0550

AC XY:

19843

AN XY:

360494

show subpopulations

Gnomad4 AFR exome

AF:

0.00660

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.0638

Gnomad4 EAS exome

AF:

0.0000995

Gnomad4 SAS exome

AF:

0.0215

Gnomad4 FIN exome

AF:

0.0849

Gnomad4 NFE exome

AF:

0.0632

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0406

AC:

4518

AN:

111180

Hom.:

Cov.:

AF XY:

0.0398

AC XY:

1330

AN XY:

33376

show subpopulations

Gnomad4 AFR

AF:

0.00908

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0638

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.0809

Gnomad4 NFE

AF:

0.0595

Gnomad4 OTH

AF:

0.0424

Alfa

AF:

0.0536

Hom.:

844

Bravo

AF:

0.0358

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 26, 2013

Eurofins Ntd Llc (ga)

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

-0.48

CADD

Benign

DANN

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00025

dbscSNV1_RF

Benign

0.0060

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over