rs2044117

Variant names:

• chr13-101055958-G-A
• rs2044117
• NM_052867.4:c.5024-470C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-101055958-G-A
• chr13-101055958-G-C
• chr13-101055958-G-T

Variant summary

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

The NM_052867.4(NALCN):​c.5024-470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,136 control chromosomes in the GnomAD database, including 2,839 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 0.19 (2839 hom., cov: 32)
• Consequence: NALCN NM_052867.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.199
• Publications: 19 publications found

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]

NALCN-AS1 (HGNC:42743): (NALCN antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALCN	NM_052867.4	c.5024-470C>T		intron_variant	Intron 43 of 43	ENST00000251127.11	NP_443099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NALCN	ENST00000251127.11	c.5024-470C>T		intron_variant	Intron 43 of 43	1	NM_052867.4	ENSP00000251127.6

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28269 AN: 152018 Hom.: 2839 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.186 AC: 28276 AN: 152136 Hom.: 2839 Cov.: 32 AF XY: 0.180 AC XY: 13402 AN XY: 74374

African (AFR) AF: 0.156 AC: 6467 AN: 41480

American (AMR) AF: 0.137 AC: 2091 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.00599 AC: 31 AN: 5174

South Asian (SAS) AF: 0.121 AC: 584 AN: 4826

European-Finnish (FIN) AF: 0.188 AC: 1992 AN: 10590

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15904 AN: 67994

Other (OTH) AF: 0.185 AC: 391 AN: 2112

Alfa AF: 0.205 Hom.: 9922

Bravo AF: 0.179

Asia WGS AF: 0.0840 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		0.20
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: rs2044117; hg19: chr13-101708310;