NM_138448.4:c.186-28913G>A

Variant names:

• chr2-54275775-G-A
• rs843748
• NM_138448.4:c.186-28913G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138448.4(ACYP2):​c.186-28913G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,988 control chromosomes in the GnomAD database, including 11,827 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 0.36 (11827 hom., cov: 32)
• Consequence: ACYP2 NM_138448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 11 publications found

Genes affected

ACYP2 (HGNC:180): (acylphosphatase 2) Acylphosphatase can hydrolyze the phosphoenzyme intermediate of different membrane pumps, particularly the Ca2+/Mg2+-ATPase from sarcoplasmic reticulum of skeletal muscle. Two isoenzymes have been isolated, called muscle acylphosphatase and erythrocyte acylphosphatase on the basis of their tissue localization. This gene encodes the muscle-type isoform (MT). An increase of the MT isoform is associated with muscle differentiation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2016]

LOC105374610 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138448.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACYP2	NM_138448.4	MANE Select	c.186-28913G>A		intron	N/A	NP_612457.1
	ACYP2	NM_001320586.2		c.405-28913G>A		intron	N/A	NP_001307515.1
	ACYP2	NM_001320587.2		c.312-28913G>A		intron	N/A	NP_001307516.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACYP2	ENST00000394666.9	TSL:1 MANE Select	c.186-28913G>A		intron	N/A	ENSP00000378161.3
	ACYP2	ENST00000607452.6	TSL:2	c.405-28913G>A		intron	N/A	ENSP00000475986.1
	ACYP2	ENST00000606865.1	TSL:5	c.138-28913G>A		intron	N/A	ENSP00000475333.1

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55404 AN: 151870 Hom.: 11825 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.365 AC: 55405 AN: 151988 Hom.: 11827 Cov.: 32 AF XY: 0.365 AC XY: 27079 AN XY: 74282

African (AFR) AF: 0.149 AC: 6173 AN: 41496

American (AMR) AF: 0.403 AC: 6159 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3464

East Asian (EAS) AF: 0.210 AC: 1089 AN: 5186

South Asian (SAS) AF: 0.292 AC: 1406 AN: 4820

European-Finnish (FIN) AF: 0.538 AC: 5667 AN: 10534

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32516 AN: 67904

Other (OTH) AF: 0.344 AC: 725 AN: 2108

Alfa AF: 0.433 Hom.: 61272

Bravo AF: 0.347

Asia WGS AF: 0.243 AC: 844 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.77
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs843748; hg19: chr2-54502912;