rs11796927

Variant names:

• chrX-49232109-T-C
• rs11796927
• NM_001256789.3:c.26-182A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-49232109-T-C
• chrX-49232109-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.91
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3	c.26-182A>G		intron_variant	Intron 1 of 47	ENST00000323022.10	NP_001243718.1
CACNA1F	NM_005183.4	c.26-182A>G		intron_variant	Intron 1 of 47		NP_005174.2
CACNA1F	NM_001256790.3	c.66-417A>G		intron_variant	Intron 1 of 47		NP_001243719.1
CACNA1F	XM_011543983.3	c.66-417A>G		intron_variant	Intron 1 of 46		XP_011542285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10	c.26-182A>G		intron_variant	Intron 1 of 47	1	NM_001256789.3	ENSP00000321618.6
CACNA1F	ENST00000376265.2	c.26-182A>G		intron_variant	Intron 1 of 47	1		ENSP00000365441.2
CACNA1F	ENST00000376251.5	c.66-417A>G		intron_variant	Intron 1 of 47	1		ENSP00000365427.1

Frequencies

GnomAD3 genomes AF: 0.0508 AC: 5589 AN: 110109 Hom.: 176 Cov.: 22

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

African (AFR) AF: 0.0113 AC: 343 AN: 30264

American (AMR) AF: 0.0394 AC: 408 AN: 10348

Ashkenazi Jewish (ASJ) AF: 0.0549 AC: 144 AN: 2621

East Asian (EAS) AF: 0.000286 AC: 1 AN: 3501

South Asian (SAS) AF: 0.0133 AC: 35 AN: 2635

European-Finnish (FIN) AF: 0.0684 AC: 393 AN: 5742

Middle Eastern (MID) AF: 0.0472 AC: 10 AN: 212

European-Non Finnish (NFE) AF: 0.0786 AC: 4138 AN: 52661

Other (OTH) AF: 0.0573 AC: 86 AN: 1500

Alfa AF: 0.0720 Hom.: 3205

Bravo AF: 0.0480

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

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	-0.80
CADD	Benign	9.0
DANN	Benign	0.68
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11796927; hg19: chrX-49088571;