chrX-49205282-C-T

Position:

chrX-49205282-C-T

Variant summary

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

The NM_001256789.3(CACNA1F):c.5756G>A(p.Arg1919His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0882 in 1,206,688 control chromosomes in the GnomAD database, including 3,568 homozygotes. There are 36,726 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 252 hom., 2164 hem., cov: 22)

Exomes 𝑓: 0.090 ( 3316 hom. 34562 hem. )

Consequence

CACNA1F
NM_001256789.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.47

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 (MetaRNN=0.0017129481).

BP6

Variant X-49205282-C-T is Benign according to our data. Variant chrX-49205282-C-T is described in ClinVar as [Benign]. Clinvar id is 100576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-49205282-C-T is described in Lovd as [Benign]. Variant chrX-49205282-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1F	NM_001256789.3 linkuse as main transcript	c.5756G>A	p.Arg1919His	missense_variant	48/48	ENST00000323022.10	NP_001243718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10 linkuse as main transcript	c.5756G>A	p.Arg1919His	missense_variant	48/48	1	NM_001256789.3	ENSP00000321618		O60840-2
CACNA1F	ENST00000376265.2 linkuse as main transcript	c.5789G>A	p.Arg1930His	missense_variant	48/48	1		ENSP00000365441	P1	O60840-1
CACNA1F	ENST00000376251.5 linkuse as main transcript	c.5594G>A	p.Arg1865His	missense_variant	48/48	1		ENSP00000365427		O60840-4

Frequencies

GnomAD3 genomes

AF:

0.0668

AC:

7369

AN:

110233

Hom.:

252

Cov.:

AF XY:

0.0665

AC XY:

2162

AN XY:

32515

show subpopulations

Gnomad AFR

AF:

0.0209

Gnomad AMI

AF:

0.00590

Gnomad AMR

AF:

0.0536

Gnomad ASJ

AF:

0.0782

Gnomad EAS

AF:

0.186

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.0744

Gnomad MID

AF:

0.0297

Gnomad NFE

AF:

0.0801

Gnomad OTH

AF:

0.0660

GnomAD3 exomes

AF:

0.0979

AC:

17653

AN:

180387

Hom.:

640

AF XY:

0.105

AC XY:

6860

AN XY:

65277

show subpopulations

Gnomad AFR exome

AF:

0.0193

Gnomad AMR exome

AF:

0.0680

Gnomad ASJ exome

AF:

0.0761

Gnomad EAS exome

AF:

0.188

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0826

Gnomad NFE exome

AF:

0.0811

Gnomad OTH exome

AF:

0.0843

GnomAD4 exome

AF:

0.0903

AC:

99025

AN:

1096402

Hom.:

3316

Cov.:

AF XY:

0.0955

AC XY:

34562

AN XY:

361860

show subpopulations

Gnomad4 AFR exome

AF:

0.0214

Gnomad4 AMR exome

AF:

0.0659

Gnomad4 ASJ exome

AF:

0.0754

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.219

Gnomad4 FIN exome

AF:

0.0831

Gnomad4 NFE exome

AF:

0.0824

Gnomad4 OTH exome

AF:

0.0897

GnomAD4 genome

AF:

0.0668

AC:

7362

AN:

110286

Hom.:

252

Cov.:

AF XY:

0.0664

AC XY:

2164

AN XY:

32578

show subpopulations

Gnomad4 AFR

AF:

0.0208

Gnomad4 AMR

AF:

0.0540

Gnomad4 ASJ

AF:

0.0782

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.0744

Gnomad4 NFE

AF:

0.0801

Gnomad4 OTH

AF:

0.0651

Alfa

AF:

0.0794

Hom.:

4376

Bravo

AF:

0.0614

TwinsUK

AF:

0.0790

AC:

293

ALSPAC

AF:

0.0848

AC:

245

ESP6500AA

AF:

0.0214

AC:

ESP6500EA

AF:

0.0846

AC:

569

ExAC

AF:

0.103

AC:

12483

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	literature only	NEI Ophthalmic Genomics Laboratory, National Institutes of Health	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.051

.;.;T

FATHMM_MKL

Benign

0.33

LIST_S2

Uncertain

0.90

D;D;D

MetaRNN

Benign

0.0017

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.99

.;.;N

MutationTaster

Benign

0.98

P;P;P

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.23

N;N;N

REVEL

Benign

0.051

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.29

T;T;T

Polyphen

0.0010

.;.;B

Vest4

0.031

MPC

0.28

ClinPred

0.013

GERP RS

1.1

Varity_R

0.044

gMVP

0.65

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

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