12-50077326-C-T

Variant names:

• chr12-50077326-C-T
• rs61731226
• NM_001095.4:c.672C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001095.4(ASIC1):​c.672C>T​(p.Ile224Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0053 in 1,614,170 control chromosomes in the GnomAD database, including 407 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (208 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (199 hom.)
• Consequence: ASIC1 NM_001095.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.130
• Publications: 1 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.082).
• BP6: Variant 12-50077326-C-T is Benign according to our data. Variant chr12-50077326-C-T is described in ClinVar as Benign. ClinVar VariationId is 783660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0943 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	NM_001095.4	MANE Select	c.672C>T	p.Ile224Ile	synonymous	Exon 4 of 12	NP_001086.2
	ASIC1	NM_020039.4		c.672C>T	p.Ile224Ile	synonymous	Exon 4 of 12	NP_064423.2
	ASIC1	NM_001256830.2		c.774C>T	p.Ile258Ile	synonymous	Exon 2 of 10	NP_001243759.1	P78348-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	ENST00000447966.7	TSL:1 MANE Select	c.672C>T	p.Ile224Ile	synonymous	Exon 4 of 12	ENSP00000400228.3	P78348-2
	ASIC1	ENST00000228468.8	TSL:1	c.672C>T	p.Ile224Ile	synonymous	Exon 4 of 12	ENSP00000228468.4	P78348-1
	ASIC1	ENST00000552438.5	TSL:1	c.774C>T	p.Ile258Ile	synonymous	Exon 2 of 10	ENSP00000450247.1	P78348-3

Frequencies

GnomAD3 genomes AF: 0.0280 AC: 4262 AN: 152184 Hom.: 207 Cov.: 32

Gnomad AFR AF: 0.0967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0133

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: 0.0191

GnomAD2 exomes AF: 0.00736 AC: 1850 AN: 251312 AF XY: 0.00488

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.00382

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000167

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00293 AC: 4281 AN: 1461868 Hom.: 199 Cov.: 31 AF XY: 0.00247 AC XY: 1798 AN XY: 727238

African (AFR) AF: 0.105 AC: 3528 AN: 33480

American (AMR) AF: 0.00492 AC: 220 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000243 AC: 21 AN: 86256

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53416

Middle Eastern (MID) AF: 0.00364 AC: 21 AN: 5768

European-Non Finnish (NFE) AF: 0.0000728 AC: 81 AN: 1112002

Other (OTH) AF: 0.00667 AC: 403 AN: 60394

GnomAD4 genome AF: 0.0281 AC: 4280 AN: 152302 Hom.: 208 Cov.: 32 AF XY: 0.0274 AC XY: 2037 AN XY: 74470

African (AFR) AF: 0.0968 AC: 4024 AN: 41550

American (AMR) AF: 0.0133 AC: 204 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68028

Other (OTH) AF: 0.0189 AC: 40 AN: 2116

Alfa AF: 0.0140 Hom.: 41

Bravo AF: 0.0318

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.27
CADD	Benign	9.0
DANN	Benign	0.85
PhyloP100		-0.13
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61731226; hg19: chr12-50471109;