rs1974771

chr2-54051406-G-Achr2-54051406-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001320586.2(ACYP2):c.155+356G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 727,612 control chromosomes in the GnomAD database, including 5,027 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 0.096 (795 hom., cov: 32)
  • Exomes 𝑓: 0.11 (4232 hom.)
• Consequence: ACYP2 NM_001320586.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.46

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]

HMGB1P31 (HGNC:39122): (high mobility group box 1 pseudogene 31)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACYP2	NM_001320586.2	c.155+356G>A		intron_variant		ENST00000607452.6
ACYP2	NM_001320587.2	c.63-5833G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACYP2	ENST00000607452.6	c.155+356G>A		intron_variant		2	NM_001320586.2
HMGB1P31	ENST00000437242.1	n.73G>A		non_coding_transcript_exon_variant	1/1
ACYP2	ENST00000422521.2	c.155+356G>A		intron_variant		5
ACYP2	ENST00000458030.3	n.675+356G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 14590 AN: 152034 Hom.: 792 Cov.: 32

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.0856

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.115 AC: 65942 AN: 575460 Hom.: 4232 Cov.: 0 AF XY: 0.112 AC XY: 35378 AN XY: 314578

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.0950

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.0788

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.106

GnomAD4 genome AF: 0.0960 AC: 14607 AN: 152152 Hom.: 795 Cov.: 32 AF XY: 0.0986 AC XY: 7335 AN XY: 74368

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.0863

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.113

Alfa AF: 0.0644 Hom.: 91

Bravo AF: 0.0929

Asia WGS AF: 0.167 AC: 581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
Cadd	Benign	1.3
Dann	Benign	0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1974771; hg19: chr2-54278543; COSMIC: COSV69707046;