NM_018674.6:c.582+4098A>G

Variant names:

• chr2-219519404-A-G
• rs746233
• NM_018674.6:c.582+4098A>G

Variant summary

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

The NM_018674.6(ASIC4):​c.582+4098A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 152,042 control chromosomes in the GnomAD database, including 24,141 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 0.56 (24141 hom., cov: 33)
• Consequence: ASIC4 NM_018674.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.406
• Publications: 15 publications found

Genes affected

ASIC4 (HGNC:21263): (acid sensing ion channel subunit family member 4) This gene belongs to the superfamily of acid-sensing ion channels, which are proton-gated, amiloride-sensitive sodium channels. These channels have been implicated in synaptic transmission, pain perception as well as mechanoperception. This gene is predominantly expressed in the pituitary gland, and was considered a candidate for paroxysmal dystonic choreoathetosis (PDC), a movement disorder, however, no correlation was found between mutations in this gene and PDC. [provided by RefSeq, Feb 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ASIC4	NM_018674.6	c.582+4098A>G		intron_variant	Intron 1 of 9	ENST00000358078.5	NP_061144.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ASIC4	ENST00000358078.5	c.582+4098A>G		intron_variant	Intron 1 of 9	5	NM_018674.6	ENSP00000350786.5

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84941 AN: 151924 Hom.: 24114 Cov.: 33

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.546

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.559 AC: 85017 AN: 152042 Hom.: 24141 Cov.: 33 AF XY: 0.556 AC XY: 41310 AN XY: 74296

African (AFR) AF: 0.634 AC: 26305 AN: 41478

American (AMR) AF: 0.539 AC: 8237 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3466

East Asian (EAS) AF: 0.304 AC: 1572 AN: 5166

South Asian (SAS) AF: 0.611 AC: 2948 AN: 4824

European-Finnish (FIN) AF: 0.503 AC: 5306 AN: 10540

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.546 AC: 37091 AN: 67968

Other (OTH) AF: 0.559 AC: 1182 AN: 2114

Alfa AF: 0.548 Hom.: 40217

Bravo AF: 0.559

Asia WGS AF: 0.488 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.81
DANN	Benign	0.44
PhyloP100		-0.41
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: rs746233; hg19: chr2-220384126;