Variant chrX-49205209-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001256789.3(CACNA1F):c.5829C>T(p.Asp1943Asp) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.72

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:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 136 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1F	NM_001256789.3 linkuse as main transcript	c.5829C>T	p.Asp1943Asp	synonymous_variant	48/48	ENST00000323022.10	NP_001243718.1	O60840-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CACNA1F	ENST00000323022.10 linkuse as main transcript	c.5829C>T	p.Asp1943Asp	synonymous_variant	48/48	1	NM_001256789.3	ENSP00000321618.6	O60840-2
CACNA1F	ENST00000376265.2 linkuse as main transcript	c.5862C>T	p.Asp1954Asp	synonymous_variant	48/48	1		ENSP00000365441.2	O60840-1
CACNA1F	ENST00000376251.5 linkuse as main transcript	c.5667C>T	p.Asp1889Asp	synonymous_variant	48/48	1		ENSP00000365427.1	O60840-4

Frequencies

GnomAD3 genomes

AF:

0.00395

AC:

441

AN:

111740

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

136

AN XY:

33896

show subpopulations

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.:

AF XY:

0.00477

AC XY:

318

AN XY:

66699

show subpopulations

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.:

Cov.:

AF XY:

0.00591

AC XY:

2144

AN XY:

362695

show subpopulations

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.:

Cov.:

AF XY:

0.00401

AC XY:

136

AN XY:

33957

show subpopulations

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.:

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

LINK: link

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

Labcorp Genetics (formerly Invitae), Labcorp

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

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