X-49205209-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001256789.3(CACNA1F):c.5829C>T(p.Asp1943=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.006 in 1,209,072 control chromosomes in the GnomAD database, including 20 homozygotes. There are 2,280 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., 136 hem., cov: 22)
  • Exomes 𝑓: 0.0062 (20 hom. 2144 hem.)
• Consequence: CACNA1F NM_001256789.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.72

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant X-49205209-G-A is Benign according to our data. Variant chrX-49205209-G-A is described in ClinVar as [Benign]. Clinvar id is 282023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.72 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00394 (441/111791) while in subpopulation NFE AF= 0.0055 (292/53093). AF 95% confidence interval is 0.00498. There are 0 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
• BS2: High Hemizygotes in GnomAd at 136 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1F	NM_001256789.3	c.5829C>T	p.Asp1943=	synonymous_variant	48/48	ENST00000323022.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.5829C>T	p.Asp1943=	synonymous_variant	48/48	1	NM_001256789.3
CACNA1F	ENST00000376265.2	c.5862C>T	p.Asp1954=	synonymous_variant	48/48	1		P1
CACNA1F	ENST00000376251.5	c.5667C>T	p.Asp1889=	synonymous_variant	48/48	1

Frequencies

GnomAD3 genomes AF: 0.00395 AC: 441 AN: 111740 Hom.: 0 Cov.: 22 AF XY: 0.00401 AC XY: 136 AN XY: 33896

Gnomad AFR AF: 0.000878

Gnomad AMI AF: 0.0103

Gnomad AMR AF: 0.000855

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0173

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00550

Gnomad OTH AF: 0.000668

GnomAD3 exomes AF: 0.00512 AC: 932 AN: 181957 Hom.: 0 AF XY: 0.00477 AC XY: 318 AN XY: 66699

Gnomad AFR exome AF: 0.000689

Gnomad AMR exome AF: 0.000804

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0200

Gnomad NFE exome AF: 0.00695

Gnomad OTH exome AF: 0.00466

GnomAD4 exome AF: 0.00620 AC: 6808 AN: 1097281 Hom.: 20 Cov.: 30 AF XY: 0.00591 AC XY: 2144 AN XY: 362695

Gnomad4 AFR exome AF: 0.000417

Gnomad4 AMR exome AF: 0.000853

Gnomad4 ASJ exome AF: 0.000258

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000370

Gnomad4 FIN exome AF: 0.0189

Gnomad4 NFE exome AF: 0.00689

Gnomad4 OTH exome AF: 0.00432

GnomAD4 genome AF: 0.00394 AC: 441 AN: 111791 Hom.: 0 Cov.: 22 AF XY: 0.00401 AC XY: 136 AN XY: 33957

Gnomad4 AFR AF: 0.000876

Gnomad4 AMR AF: 0.000853

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0173

Gnomad4 NFE AF: 0.00550

Gnomad4 OTH AF: 0.000660

Alfa AF: 0.00381 Hom.: 29

Bravo AF: 0.00293

EpiCase AF: 0.00523

EpiControl AF: 0.00743

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 07, 2015

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.037
Dann	Benign	0.89

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: rs138189763; hg19: chrX-49061669;