chr12-50068355-T-C

Variant names:

• chr12-50068355-T-C
• rs10875995
• NM_001095.4:c.558+8401T>C

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+8401T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 152,122 control chromosomes in the GnomAD database, including 6,059 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 0.27 (6059 hom., cov: 31)
• Consequence: ASIC1 NM_001095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 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+8401T>C		intron	N/A	NP_001086.2
	ASIC1	NM_020039.4		c.558+8401T>C		intron	N/A	NP_064423.2
	ASIC1	NM_001412756.1		c.558+8401T>C		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+8401T>C		intron	N/A	ENSP00000400228.3
	ASIC1	ENST00000228468.8	TSL:1	c.558+8401T>C		intron	N/A	ENSP00000228468.4
	ASIC1	ENST00000453327.7	TSL:2	c.66+8401T>C		intron	N/A	ENSP00000402896.3

Frequencies

GnomAD3 genomes AF: 0.267 AC: 40606 AN: 152004 Hom.: 6062 Cov.: 31

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.00749

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.267 AC: 40606 AN: 152122 Hom.: 6059 Cov.: 31 AF XY: 0.261 AC XY: 19410 AN XY: 74366

African (AFR) AF: 0.191 AC: 7930 AN: 41466

American (AMR) AF: 0.193 AC: 2952 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 574 AN: 3464

East Asian (EAS) AF: 0.00770 AC: 40 AN: 5194

South Asian (SAS) AF: 0.331 AC: 1595 AN: 4816

European-Finnish (FIN) AF: 0.286 AC: 3030 AN: 10582

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23638 AN: 67986

Other (OTH) AF: 0.251 AC: 530 AN: 2114

Alfa AF: 0.308 Hom.: 12310

Bravo AF: 0.253

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.43
PhyloP100		-1.0
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: rs10875995; hg19: chr12-50462138;