rs10494541

Variant names:

• chr1-181581329-A-G
• rs10494541
• NM_001205293.3:c.951+553A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-181581329-A-G
• chr1-181581329-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001205293.3(CACNA1E):​c.951+553A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 152,168 control chromosomes in the GnomAD database, including 52,215 homozygotes. 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 0.82 (52215 hom., cov: 32)
• Consequence: CACNA1E NM_001205293.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.700
• Publications: 5 publications found

Genes affected

CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CACNA1E Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 69

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.951+553A>G		intron_variant	Intron 6 of 47	ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367573.7	c.951+553A>G		intron_variant	Intron 6 of 47	1	NM_001205293.3	ENSP00000356545.2
CACNA1E	ENST00000360108.7	c.951+553A>G		intron_variant	Intron 6 of 46	5		ENSP00000353222.3
CACNA1E	ENST00000367570.6	c.951+553A>G		intron_variant	Intron 6 of 46	1		ENSP00000356542.1
CACNA1E	ENST00000621791.4	c.951+553A>G		intron_variant	Intron 6 of 45	1		ENSP00000481619.1
CACNA1E	ENST00000524607.6	c.1386+553A>G		intron_variant	Intron 8 of 11	5		ENSP00000432038.2

Frequencies

GnomAD3 genomes AF: 0.821 AC: 124779 AN: 152050 Hom.: 52183 Cov.: 32

Gnomad AFR AF: 0.648

Gnomad AMI AF: 0.928

Gnomad AMR AF: 0.881

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.976

Gnomad SAS AF: 0.842

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.866

Gnomad NFE AF: 0.880

Gnomad OTH AF: 0.837

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.821 AC: 124864 AN: 152168 Hom.: 52215 Cov.: 32 AF XY: 0.825 AC XY: 61431 AN XY: 74422

African (AFR) AF: 0.648 AC: 26881 AN: 41468

American (AMR) AF: 0.881 AC: 13477 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3219 AN: 3472

East Asian (EAS) AF: 0.976 AC: 5063 AN: 5186

South Asian (SAS) AF: 0.844 AC: 4064 AN: 4818

European-Finnish (FIN) AF: 0.888 AC: 9423 AN: 10614

Middle Eastern (MID) AF: 0.866 AC: 253 AN: 292

European-Non Finnish (NFE) AF: 0.880 AC: 59868 AN: 67998

Other (OTH) AF: 0.839 AC: 1770 AN: 2110

Alfa AF: 0.864 Hom.: 98070

Bravo AF: 0.814

Asia WGS AF: 0.896 AC: 3113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.8
DANN	Benign	0.49
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10494541; hg19: chr1-181550465;