12-50080489-C-T

Position:

• chr12-50080489-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001095.4(ASIC1):​c.1206-9C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00376 in 1,613,646 control chromosomes in the GnomAD database, including 206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (109 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (97 hom.)
• Consequence: ASIC1 NM_001095.4 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0005725
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.934

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-50080489-C-T is Benign according to our data. Variant chr12-50080489-C-T is described in ClinVar as [Benign]. Clinvar id is 784239.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASIC1	NM_001095.4	c.1206-9C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000447966.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASIC1	ENST00000447966.7	c.1206-9C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001095.4	P1

Frequencies

GnomAD3 genomes AF: 0.0200 AC: 3038 AN: 152142 Hom.: 109 Cov.: 33

Gnomad AFR AF: 0.0688

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00949

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0158

GnomAD3 exomes AF: 0.00504 AC: 1265 AN: 251194 Hom.: 41 AF XY: 0.00330 AC XY: 448 AN XY: 135768

Gnomad AFR exome AF: 0.0704

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000880

Gnomad OTH exome AF: 0.00228

GnomAD4 exome AF: 0.00207 AC: 3020 AN: 1461386 Hom.: 97 Cov.: 31 AF XY: 0.00173 AC XY: 1256 AN XY: 727014

Gnomad4 AFR exome AF: 0.0748

Gnomad4 AMR exome AF: 0.00335

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000139

Gnomad4 FIN exome AF: 0.0000749

Gnomad4 NFE exome AF: 0.0000450

Gnomad4 OTH exome AF: 0.00480

GnomAD4 genome AF: 0.0200 AC: 3052 AN: 152260 Hom.: 109 Cov.: 33 AF XY: 0.0198 AC XY: 1471 AN XY: 74450

Gnomad4 AFR AF: 0.0689

Gnomad4 AMR AF: 0.00948

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00504 Hom.: 16

Bravo AF: 0.0230

Asia WGS AF: 0.00404 AC: 14 AN: 3476

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 24, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.81

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00057
dbscSNV1_RF	Benign	0.30
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: rs74090047; hg19: chr12-50474272;