rs1108923

Positions:

• chr12-50064313-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001095.4(ASIC1):​c.558+4359G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,160 control chromosomes in the GnomAD database, including 1,558 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 0.12 (1558 hom., cov: 32)
• Consequence: ASIC1 NM_001095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53

Genes affected

ASIC1 (HGNC:100): (acid sensing ion channel subunit 1) This gene encodes a member of the acid-sensing ion channel (ASIC) family of proteins, which are part of the degenerin/epithelial sodium channel (DEG/ENaC) superfamily. Members of the ASIC family are sensitive to amiloride and function in neurotransmission. The encoded proteins function in learning, pain transduction, touch sensation, and development of memory and fear. Alternatively spliced transcript variants have been described. [provided by RefSeq, Feb 2012]

ASIC1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.558+4359G>T		intron_variant		ENST00000447966.7	NP_001086.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ASIC1	ENST00000447966.7	c.558+4359G>T		intron_variant		1	NM_001095.4	ENSP00000400228.3
ASIC1	ENST00000228468.8	c.558+4359G>T		intron_variant		1		ENSP00000228468.4
ASIC1	ENST00000453327.7	c.66+4359G>T		intron_variant		2		ENSP00000402896.3
ASIC1	ENST00000550558.5	n.558+4359G>T		intron_variant		2		ENSP00000448263.1

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18938 AN: 152042 Hom.: 1558 Cov.: 32

Gnomad AFR AF: 0.0362

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0921

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.124 AC: 18933 AN: 152160 Hom.: 1558 Cov.: 32 AF XY: 0.121 AC XY: 8992 AN XY: 74382

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.121

Alfa AF: 0.152 Hom.: 921

Bravo AF: 0.114

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.82

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: rs1108923; hg19: chr12-50458096;