chrX-49212906-T-C

Variant names:

• chrX-49212906-T-C
• rs2071316
• NM_001256789.3:c.3813+68A>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.3813+68A>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 0.64 (16365 hom., 19853 hem., cov: 21)
  • Exomes 𝑓: 0.68 (167935 hom. 231952 hem.)
  • Failed GnomAD Quality Control
• Consequence: CACNA1F NM_001256789.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.673
• Publications: 10 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=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1F	NM_001256789.3	c.3813+68A>G		intron_variant	Intron 32 of 47	ENST00000323022.10	NP_001243718.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1F	ENST00000323022.10	c.3813+68A>G		intron_variant	Intron 32 of 47	1	NM_001256789.3	ENSP00000321618.6
CACNA1F	ENST00000376265.2	c.3846+68A>G		intron_variant	Intron 32 of 47	1		ENSP00000365441.2
CACNA1F	ENST00000376251.5	c.3651+68A>G		intron_variant	Intron 32 of 47	1		ENSP00000365427.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 69597 AN: 109435 Hom.: 16373 Cov.: 21

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.620

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.716

Gnomad NFE AF: 0.701

Gnomad OTH AF: 0.639

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.680 AC: 722129 AN: 1061603 Hom.: 167935 Cov.: 25 AF XY: 0.694 AC XY: 231952 AN XY: 334185

African (AFR) AF: 0.590 AC: 15139 AN: 25648

American (AMR) AF: 0.399 AC: 13181 AN: 33003

Ashkenazi Jewish (ASJ) AF: 0.777 AC: 14764 AN: 18992

East Asian (EAS) AF: 0.347 AC: 10219 AN: 29453

South Asian (SAS) AF: 0.700 AC: 36172 AN: 51708

European-Finnish (FIN) AF: 0.637 AC: 25352 AN: 39778

Middle Eastern (MID) AF: 0.718 AC: 2912 AN: 4057

European-Non Finnish (NFE) AF: 0.706 AC: 574428 AN: 814057

Other (OTH) AF: 0.667 AC: 29962 AN: 44907

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.636 AC: 69622 AN: 109490 Hom.: 16365 Cov.: 21 AF XY: 0.624 AC XY: 19853 AN XY: 31812

African (AFR) AF: 0.592 AC: 17783 AN: 30017

American (AMR) AF: 0.485 AC: 4997 AN: 10311

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2081 AN: 2629

East Asian (EAS) AF: 0.337 AC: 1167 AN: 3461

South Asian (SAS) AF: 0.676 AC: 1675 AN: 2477

European-Finnish (FIN) AF: 0.626 AC: 3560 AN: 5686

Middle Eastern (MID) AF: 0.706 AC: 149 AN: 211

European-Non Finnish (NFE) AF: 0.701 AC: 36835 AN: 52531

Other (OTH) AF: 0.641 AC: 956 AN: 1491

Alfa AF: 0.676 Hom.: 92268

Bravo AF: 0.617

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.35
PhyloP100		-0.67

Splicing

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

Other links and lift over

dbSNP: rs2071316; hg19: chrX-49069366;