X-49231025-A-G

Position:

• chrX-49231025-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001256789.3(CACNA1F):​c.382-36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.64 (16505 hom., 15315 hem., cov: 18)
  • Exomes 𝑓: 0.68 (154208 hom. 189773 hem.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1F NM_001256789.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CACNA1F	NM_001256789.3	c.382-36T>C		intron_variant		ENST00000323022.10
CACNA1F	NM_001256790.3	c.187-36T>C		intron_variant
CACNA1F	NM_005183.4	c.382-36T>C		intron_variant
CACNA1F	XM_011543983.3	c.187-36T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CACNA1F	ENST00000323022.10	c.382-36T>C		intron_variant		1	NM_001256789.3
CACNA1F	ENST00000376251.5	c.187-36T>C		intron_variant		1
CACNA1F	ENST00000376265.2	c.382-36T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 65030 AN: 101992 Hom.: 16512 Cov.: 18 AF XY: 0.603 AC XY: 15271 AN XY: 25318

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.532

Gnomad ASJ AF: 0.788

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.641

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.681 AC: 630167 AN: 925689 Hom.: 154208 Cov.: 16 AF XY: 0.678 AC XY: 189773 AN XY: 279755

Gnomad4 AFR exome AF: 0.544

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.775

Gnomad4 EAS exome AF: 0.344

Gnomad4 SAS exome AF: 0.697

Gnomad4 FIN exome AF: 0.653

Gnomad4 NFE exome AF: 0.708

Gnomad4 OTH exome AF: 0.668

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.638 AC: 65055 AN: 102037 Hom.: 16505 Cov.: 18 AF XY: 0.604 AC XY: 15315 AN XY: 25375

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.532

Gnomad4 ASJ AF: 0.788

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.620

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.644

Alfa AF: 0.593 Hom.: 5504

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5905724; hg19: chrX-49087487;