12-50064313-G-T

Variant names:

• chr12-50064313-G-T
• rs1108923
• NM_001095.4:c.558+4359G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001095.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	NM_001095.4	MANE Select	c.558+4359G>T		intron	N/A	NP_001086.2
	ASIC1	NM_020039.4		c.558+4359G>T		intron	N/A	NP_064423.2
	ASIC1	NM_001412756.1		c.558+4359G>T		intron	N/A	NP_001399685.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	ENST00000447966.7	TSL:1 MANE Select	c.558+4359G>T		intron	N/A	ENSP00000400228.3
	ASIC1	ENST00000228468.8	TSL:1	c.558+4359G>T		intron	N/A	ENSP00000228468.4
	ASIC1	ENST00000453327.7	TSL:2	c.66+4359G>T		intron	N/A	ENSP00000402896.3

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

African (AFR) AF: 0.0360 AC: 1497 AN: 41530

American (AMR) AF: 0.0919 AC: 1405 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5178

South Asian (SAS) AF: 0.104 AC: 501 AN: 4822

European-Finnish (FIN) AF: 0.172 AC: 1820 AN: 10582

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13020 AN: 67974

Other (OTH) AF: 0.121 AC: 255 AN: 2108

Alfa AF: 0.153 Hom.: 1071

Bravo AF: 0.114

Asia WGS AF: 0.0420 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	7.9
DANN	Benign	0.82
PhyloP100		1.5
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: rs1108923; hg19: chr12-50458096;