12-50080257-T-C

Position:

• chr12-50080257-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.1205+202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 782,568 control chromosomes in the GnomAD database, including 177,762 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 0.69 (36350 hom., cov: 32)
  • Exomes 𝑓: 0.67 (141412 hom.)
• Consequence: ASIC1 NM_001095.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ASIC1	NM_001095.4	c.1205+202T>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.1205+202T>C		intron_variant		1	NM_001095.4	ENSP00000400228	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104607 AN: 151940 Hom.: 36293 Cov.: 32

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.722

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.850

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.699

GnomAD4 exome AF: 0.665 AC: 419557 AN: 630510 Hom.: 141412 AF XY: 0.662 AC XY: 217416 AN XY: 328532

Gnomad4 AFR exome AF: 0.730

Gnomad4 AMR exome AF: 0.732

Gnomad4 ASJ exome AF: 0.801

Gnomad4 EAS exome AF: 0.874

Gnomad4 SAS exome AF: 0.607

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.643

Gnomad4 OTH exome AF: 0.681

GnomAD4 genome AF: 0.689 AC: 104727 AN: 152058 Hom.: 36350 Cov.: 32 AF XY: 0.695 AC XY: 51661 AN XY: 74338

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.733

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.850

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.710

Gnomad4 NFE AF: 0.639

Gnomad4 OTH AF: 0.698

Alfa AF: 0.662 Hom.: 56530

Bravo AF: 0.695

Asia WGS AF: 0.710 AC: 2466 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	5.7
DANN	Benign	0.58

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: rs376184; hg19: chr12-50474040;