rs746233

Positions:

• chr2-219519404-A-G

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
ASIC4	NM_018674.6	c.582+4098A>G		intron_variant		ENST00000358078.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC4	ENST00000358078.5	c.582+4098A>G		intron_variant		5	NM_018674.6	P1

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

Gnomad4 AFR AF: 0.634

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.546

Gnomad4 OTH AF: 0.559

Alfa AF: 0.549 Hom.: 30605

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

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

Other links and lift over

dbSNP: rs746233; hg19: chr2-220384126;