rs9518331

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000251127.11(NALCN):​c.1839+2397C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,000 control chromosomes in the GnomAD database, including 5,397 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 0.25 ( 5397 hom., cov: 32)

Consequence

NALCN
ENST00000251127.11 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.29
Variant links:
Genes affected
NALCN (HGNC:19082): (sodium leak channel, non-selective) This gene encodes a voltage-independent, nonselective cation channel which belongs to a family of voltage-gated sodium and calcium channels that regulates the resting membrane potential and excitability of neurons. This family is expressed throughout the nervous system and conducts a persistent sodium leak current that contributes to tonic neuronal excitability. The encoded protein forms a channelosome complex that includes G-protein-coupled receptors, UNC-79, UNC-80, NCA localization factor-1, and src family tyrosine kinases. Naturally occurring mutations in this gene are associated with infantile neuroaxonal dystrophy, infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) syndrome, and congenital contractures of the limbs and face with hypotonia and developmental delay (CLIFAHDD) syndrome. A knockout of the orthologous gene in mice results in paralysis with a severely disrupted respiratory rhythm, and lethality within 24 hours after birth. [provided by RefSeq, Apr 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NALCNNM_052867.4 linkuse as main transcriptc.1839+2397C>A intron_variant ENST00000251127.11 NP_443099.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NALCNENST00000251127.11 linkuse as main transcriptc.1839+2397C>A intron_variant 1 NM_052867.4 ENSP00000251127 P1Q8IZF0-1

Frequencies

GnomAD3 genomes
AF:
0.248
AC:
37683
AN:
151880
Hom.:
5398
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.144
Gnomad AMI
AF:
0.426
Gnomad AMR
AF:
0.187
Gnomad ASJ
AF:
0.262
Gnomad EAS
AF:
0.0249
Gnomad SAS
AF:
0.287
Gnomad FIN
AF:
0.309
Gnomad MID
AF:
0.206
Gnomad NFE
AF:
0.327
Gnomad OTH
AF:
0.250
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.248
AC:
37685
AN:
152000
Hom.:
5397
Cov.:
32
AF XY:
0.246
AC XY:
18240
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.144
Gnomad4 AMR
AF:
0.187
Gnomad4 ASJ
AF:
0.262
Gnomad4 EAS
AF:
0.0251
Gnomad4 SAS
AF:
0.286
Gnomad4 FIN
AF:
0.309
Gnomad4 NFE
AF:
0.327
Gnomad4 OTH
AF:
0.247
Alfa
AF:
0.286
Hom.:
801
Bravo
AF:
0.234
Asia WGS
AF:
0.162
AC:
564
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.060
DANN
Benign
0.22

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs9518331; hg19: chr13-101826254; API