12-50058844-A-G

Variant names:

• chr12-50058844-A-G
• rs74090033
• NM_001095.4:c.78A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001095.4(ASIC1):​c.78A>G​(p.Thr26Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,748 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (12 hom., cov: 32)
  • Exomes 𝑓: 0.00055 (8 hom.)
• Consequence: ASIC1 NM_001095.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.86
• Publications: 0 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 12-50058844-A-G is Benign according to our data. Variant chr12-50058844-A-G is described in ClinVar as Benign. ClinVar VariationId is 714537.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.86 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00542 (826/152284) while in subpopulation AFR AF = 0.0184 (766/41562). AF 95% confidence interval is 0.0173. There are 12 homozygotes in GnomAd4. There are 393 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 826 AD gene.

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.78A>G	p.Thr26Thr	synonymous	Exon 2 of 12	NP_001086.2
	ASIC1	NM_020039.4		c.78A>G	p.Thr26Thr	synonymous	Exon 2 of 12	NP_064423.2
	ASIC1	NM_001412756.1		c.78A>G	p.Thr26Thr	synonymous	Exon 2 of 13	NP_001399685.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ASIC1	ENST00000447966.7	TSL:1 MANE Select	c.78A>G	p.Thr26Thr	synonymous	Exon 2 of 12	ENSP00000400228.3	P78348-2
	ASIC1	ENST00000228468.8	TSL:1	c.78A>G	p.Thr26Thr	synonymous	Exon 2 of 12	ENSP00000228468.4	P78348-1
	ASIC1	ENST00000895671.1		c.78A>G	p.Thr26Thr	synonymous	Exon 2 of 13	ENSP00000565730.1

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 822 AN: 152166 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00353

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: 0.0000441

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00130 AC: 325 AN: 250716 AF XY: 0.000819

Gnomad AFR exome AF: 0.0176

Gnomad AMR exome AF: 0.000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000554 AC: 810 AN: 1461464 Hom.: 8 Cov.: 30 AF XY: 0.000477 AC XY: 347 AN XY: 726988

African (AFR) AF: 0.0199 AC: 667 AN: 33474

American (AMR) AF: 0.000872 AC: 39 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39690

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1111758

Other (OTH) AF: 0.00134 AC: 81 AN: 60382

GnomAD4 genome AF: 0.00542 AC: 826 AN: 152284 Hom.: 12 Cov.: 32 AF XY: 0.00528 AC XY: 393 AN XY: 74470

African (AFR) AF: 0.0184 AC: 766 AN: 41562

American (AMR) AF: 0.00353 AC: 54 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68012

Other (OTH) AF: 0.00142 AC: 3 AN: 2112

Alfa AF: 0.00178 Hom.: 1

Bravo AF: 0.00610

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

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
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.98
DANN	Benign	0.58
PhyloP100		-3.9
Mutation Taster		=99/1	polymorphism

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: rs74090033; hg19: chr12-50452627;