rs11796927

chrX-49232109-T-CchrX-49232109-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001256789.3(CACNA1F):c.26-182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 110,152 control chromosomes in the GnomAD database, including 175 homozygotes. There are 1,576 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.051 (175 hom., 1576 hem., cov: 22)
• Consequence: CACNA1F NM_001256789.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.91

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-49232109-T-C is Benign according to our data. Variant chrX-49232109-T-C is described in ClinVar as [Benign]. Clinvar id is 1272957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1F	NM_001256789.3	c.26-182A>G		intron_variant		ENST00000323022.10
CACNA1F	NM_001256790.3	c.66-417A>G		intron_variant
CACNA1F	NM_005183.4	c.26-182A>G		intron_variant
CACNA1F	XM_011543983.3	c.66-417A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.26-182A>G		intron_variant		1	NM_001256789.3
CACNA1F	ENST00000376251.5	c.66-417A>G		intron_variant		1
CACNA1F	ENST00000376265.2	c.26-182A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 5589 AN: 110109 Hom.: 176 Cov.: 22 AF XY: 0.0484 AC XY: 1576 AN XY: 32537

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0404

Gnomad AMR AF: 0.0395

Gnomad ASJ AF: 0.0549

Gnomad EAS AF: 0.000285

Gnomad SAS AF: 0.0140

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.0515

Gnomad NFE AF: 0.0786

Gnomad OTH AF: 0.0580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0507 AC: 5585 AN: 110152 Hom.: 175 Cov.: 22 AF XY: 0.0484 AC XY: 1576 AN XY: 32592

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.0394

Gnomad4 ASJ AF: 0.0549

Gnomad4 EAS AF: 0.000286

Gnomad4 SAS AF: 0.0133

Gnomad4 FIN AF: 0.0684

Gnomad4 NFE AF: 0.0786

Gnomad4 OTH AF: 0.0573

Alfa AF: 0.0723 Hom.: 2672

Bravo AF: 0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	9.0
Dann	Benign	0.68

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

Other links and lift over

dbSNP: rs11796927; hg19: chrX-49088571;