X-49205164-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001256789.3(CACNA1F):​c.5874C>T​(p.Asp1958=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,207,982 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.000018 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000011 ( 0 hom. 3 hem. )

Consequence

CACNA1F
NM_001256789.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.64).
BP6
Variant X-49205164-G-A is Benign according to our data. Variant chrX-49205164-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1136539.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.17 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CACNA1FNM_001256789.3 linkuse as main transcriptc.5874C>T p.Asp1958= synonymous_variant 48/48 ENST00000323022.10 NP_001243718.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CACNA1FENST00000323022.10 linkuse as main transcriptc.5874C>T p.Asp1958= synonymous_variant 48/481 NM_001256789.3 ENSP00000321618 O60840-2
CACNA1FENST00000376265.2 linkuse as main transcriptc.5907C>T p.Asp1969= synonymous_variant 48/481 ENSP00000365441 P1O60840-1
CACNA1FENST00000376251.5 linkuse as main transcriptc.5712C>T p.Asp1904= synonymous_variant 48/481 ENSP00000365427 O60840-4

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112166
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34312
show subpopulations
Gnomad AFR
AF:
0.0000324
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000940
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000550
AC:
1
AN:
181656
Hom.:
0
AF XY:
0.0000151
AC XY:
1
AN XY:
66442
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000124
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000110
AC:
12
AN:
1095816
Hom.:
0
Cov.:
30
AF XY:
0.00000830
AC XY:
3
AN XY:
361310
show subpopulations
Gnomad4 AFR exome
AF:
0.0000759
Gnomad4 AMR exome
AF:
0.0000284
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000370
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000714
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112166
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
34312
show subpopulations
Gnomad4 AFR
AF:
0.0000324
Gnomad4 AMR
AF:
0.0000940
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 04, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
0.19
DANN
Benign
0.83

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.

Other links and lift over

dbSNP: rs782497299; hg19: chrX-49061624; COSMIC: COSV104550447; COSMIC: COSV104550447; API