12-50068355-T-C

Position:

• chr12-50068355-T-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.558+8401T>C		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+8401T>C		intron_variant		1	NM_001095.4	ENSP00000400228.3
ASIC1	ENST00000228468.8	c.558+8401T>C		intron_variant		1		ENSP00000228468.4
ASIC1	ENST00000453327.7	c.66+8401T>C		intron_variant		2		ENSP00000402896.3
ASIC1	ENST00000550558.5	n.558+8401T>C		intron_variant		2		ENSP00000448263.1

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

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.00770

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.251

Alfa AF: 0.312 Hom.: 9879

Bravo AF: 0.253

Asia WGS AF: 0.177 AC: 618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.65
DANN	Benign	0.43

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: rs10875995; hg19: chr12-50462138;