rs41312124

chrX-49219318-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256789.3(CACNA1F):c.2673+3G>A variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.0002534
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.999

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]

ACMG classification

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/exons	MANE	UniProt
CACNA1F	NM_001256789.3	c.2673+3G>A		splice_donor_region_variant, intron_variant		ENST00000323022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.2673+3G>A		splice_donor_region_variant, intron_variant		1	NM_001256789.3
CACNA1F	ENST00000376251.5	c.2511+3G>A		splice_donor_region_variant, intron_variant		1
CACNA1F	ENST00000376265.2	c.2706+3G>A		splice_donor_region_variant, intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 4516 AN: 111126 Hom.: 84 Cov.: 22 AF XY: 0.0399 AC XY: 1328 AN XY: 33312

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

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.: 33 AF XY: 0.0550 AC XY: 19843 AN XY: 360494

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.: 84 Cov.: 22 AF XY: 0.0398 AC XY: 1330 AN XY: 33376

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:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 26, 2013	- -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Ocular albinism, type II Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Congenital stationary night blindness 2A Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

X-linked cone-rod dystrophy 3 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs41312124; hg19: chrX-49075777;