X-49231025-A-G

Variant names:

• chrX-49231025-A-G
• rs5905724
• NM_001256789.3:c.382-36T>C

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 8 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: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256789.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1F	NM_001256789.3	MANE Select	c.382-36T>C		intron	N/A	NP_001243718.1
	CACNA1F	NM_005183.4		c.382-36T>C		intron	N/A	NP_005174.2
	CACNA1F	NM_001256790.3		c.187-36T>C		intron	N/A	NP_001243719.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CACNA1F	ENST00000323022.10	TSL:1 MANE Select	c.382-36T>C		intron	N/A	ENSP00000321618.6
	CACNA1F	ENST00000376265.2	TSL:1	c.382-36T>C		intron	N/A	ENSP00000365441.2
	CACNA1F	ENST00000376251.5	TSL:1	c.187-36T>C		intron	N/A	ENSP00000365427.1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 65030 AN: 101992 Hom.: 16512 Cov.: 18

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

African (AFR) AF: 0.544 AC: 12663 AN: 23272

American (AMR) AF: 0.483 AC: 16232 AN: 33582

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 14009 AN: 18074

East Asian (EAS) AF: 0.344 AC: 9992 AN: 29054

South Asian (SAS) AF: 0.697 AC: 34341 AN: 49262

European-Finnish (FIN) AF: 0.653 AC: 25636 AN: 39242

Middle Eastern (MID) AF: 0.719 AC: 2697 AN: 3753

European-Non Finnish (NFE) AF: 0.708 AC: 487656 AN: 689138

Other (OTH) AF: 0.668 AC: 26941 AN: 40312

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

African (AFR) AF: 0.557 AC: 15402 AN: 27649

American (AMR) AF: 0.532 AC: 5045 AN: 9477

Ashkenazi Jewish (ASJ) AF: 0.788 AC: 1982 AN: 2515

East Asian (EAS) AF: 0.328 AC: 1051 AN: 3209

South Asian (SAS) AF: 0.662 AC: 1390 AN: 2101

European-Finnish (FIN) AF: 0.620 AC: 2913 AN: 4700

Middle Eastern (MID) AF: 0.743 AC: 150 AN: 202

European-Non Finnish (NFE) AF: 0.714 AC: 35845 AN: 50181

Other (OTH) AF: 0.644 AC: 881 AN: 1367

Alfa AF: 0.593 Hom.: 5504

Bravo AF: 0.624

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs5905724; hg19: chrX-49087487;