chrX-49231001-A-C

Variant names:

• chrX-49231001-A-C
• rs2036773529
• NM_001256789.3:c.382-12T>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001256789.3(CACNA1F):​c.382-12T>G 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 0.000011 (0 hom., 0 hem., cov: 21)
  • Exomes 𝑓: 0.0035 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1F NM_001256789.3 intron
• Scores: Splicing: ADA: 0.006070
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3	c.382-12T>G		intron_variant	Intron 3 of 47	ENST00000323022.10	NP_001243718.1
CACNA1F	NM_005183.4	c.382-12T>G		intron_variant	Intron 3 of 47		NP_005174.2
CACNA1F	NM_001256790.3	c.187-12T>G		intron_variant	Intron 3 of 47		NP_001243719.1
CACNA1F	XM_011543983.3	c.187-12T>G		intron_variant	Intron 3 of 46		XP_011542285.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10	c.382-12T>G		intron_variant	Intron 3 of 47	1	NM_001256789.3	ENSP00000321618.6
CACNA1F	ENST00000376265.2	c.382-12T>G		intron_variant	Intron 3 of 47	1		ENSP00000365441.2
CACNA1F	ENST00000376251.5	c.187-12T>G		intron_variant	Intron 3 of 47	1		ENSP00000365427.1

Frequencies

GnomAD3 genomes AF: 0.0000107 AC: 1 AN: 93818 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000211

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00346 AC: 1810 AN: 523388 Hom.: 0 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 156168

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00196 AC: 29 AN: 14767

American (AMR) AF: 0.0000659 AC: 2 AN: 30340

Ashkenazi Jewish (ASJ) AF: 0.000718 AC: 9 AN: 12539

East Asian (EAS) AF: 0.000345 AC: 6 AN: 17389

South Asian (SAS) AF: 0.000881 AC: 37 AN: 42007

European-Finnish (FIN) AF: 0.0000362 AC: 1 AN: 27662

Middle Eastern (MID) AF: 0.000728 AC: 2 AN: 2746

European-Non Finnish (NFE) AF: 0.00471 AC: 1662 AN: 352691

Other (OTH) AF: 0.00267 AC: 62 AN: 23247

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000107 AC: 1 AN: 93853 Hom.: 0 Cov.: 21 AF XY: 0.00 AC XY: 0 AN XY: 24409

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25615

American (AMR) AF: 0.00 AC: 0 AN: 8625

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2364

East Asian (EAS) AF: 0.00 AC: 0 AN: 2560

South Asian (SAS) AF: 0.00 AC: 0 AN: 1560

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3692

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.0000211 AC: 1 AN: 47349

Other (OTH) AF: 0.00 AC: 0 AN: 1273

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0061
dbscSNV1_RF	Benign	0.26
SpliceAI score (max)		0.020		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: rs2036773529; hg19: chrX-49087463;