NM_138448.4:c.58+4857C>T

Variant names:

• chr2-54120613-C-T
• rs1559040
• NM_138448.4:c.58+4857C>T

Variant summary

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

The NM_138448.4(ACYP2):​c.58+4857C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,228 control chromosomes in the GnomAD database, including 979 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 0.11 (979 hom., cov: 32)
• Consequence: ACYP2 NM_138448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 19 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACYP2	NM_138448.4	c.58+4857C>T		intron_variant	Intron 1 of 3	ENST00000394666.9	NP_612457.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACYP2	ENST00000394666.9	c.58+4857C>T		intron_variant	Intron 1 of 3	1	NM_138448.4	ENSP00000378161.3

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16785 AN: 152110 Hom.: 977 Cov.: 32

Gnomad AFR AF: 0.0926

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.110 AC: 16801 AN: 152228 Hom.: 979 Cov.: 32 AF XY: 0.109 AC XY: 8101 AN XY: 74438

African (AFR) AF: 0.0928 AC: 3856 AN: 41532

American (AMR) AF: 0.110 AC: 1684 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 508 AN: 3472

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5182

South Asian (SAS) AF: 0.0681 AC: 329 AN: 4828

European-Finnish (FIN) AF: 0.104 AC: 1099 AN: 10588

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8891 AN: 68000

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.0419 Hom.: 206

Bravo AF: 0.111

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.50
DANN	Benign	0.36
PhyloP100		-1.8
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: rs1559040; hg19: chr2-54347750;