rs145123059

Variant names:

• chr11-47242719-T-C
• rs145123059
• NM_001610.4:c.1138+4A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001610.4(ACP2):​c.1138+4A>G variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000489 in 1,609,880 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0027 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00026 (2 hom.)
• Consequence: ACP2 NM_001610.4 splice_region, intron
• Scores: Splicing: ADA: 0.9629
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.04
• Publications: 0 publications found

Genes affected

ACP2 (HGNC:123): (acid phosphatase 2, lysosomal) The protein encoded by this gene belongs to the histidine acid phosphatase family, which hydrolyze orthophosphoric monoesters to alcohol and phosphate. This protein is localized to the lysosomal membrane, and is chemically and genetically distinct from the red cell acid phosphatase. Mice lacking this gene showed multiple defects, including bone structure alterations, lysosomal storage defects, and an increased tendency towards seizures. An enzymatically-inactive allele of this gene in mice showed severe growth retardation, hair-follicle abnormalities, and an ataxia-like phenotype. Alternatively spliced transcript variants have been found for this gene. A C-terminally extended isoform is also predicted to be produced by the use of an alternative in-frame translation termination codon via a stop codon readthrough mechanism. [provided by RefSeq, Oct 2017]

ACP2 Gene-Disease associations (from GenCC):

• lysosomal acid phosphatase deficiency

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP6: Variant 11-47242719-T-C is Benign according to our data. Variant chr11-47242719-T-C is described in ClinVar as Benign. ClinVar VariationId is 780968.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 2 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001610.4. 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
	ACP2	NM_001610.4	MANE Select	c.1138+4A>G		splice_region intron	N/A	NP_001601.1	P11117-1
	ACP2	NM_001357016.2		c.1138+4A>G		splice_region intron	N/A	NP_001343945.1	A0A5F9ZHR7
	ACP2	NM_001302489.2		c.1054+4A>G		splice_region intron	N/A	NP_001289418.1	E9PQY3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP2	ENST00000672073.1	MANE Select	c.1138+4A>G		splice_region intron	N/A	ENSP00000500291.1	P11117-1
	ACP2	ENST00000256997.9	TSL:1	c.1138+4A>G		splice_region intron	N/A	ENSP00000256997.3	P11117-1
	ACP2	ENST00000672636.2		c.1138+4A>G		splice_region intron	N/A	ENSP00000500571.2	A0A5F9ZHR7

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 403 AN: 152112 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00871

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.000717 AC: 179 AN: 249766 AF XY: 0.000518

Gnomad AFR exome AF: 0.00899

Gnomad AMR exome AF: 0.000869

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000259 AC: 377 AN: 1457650 Hom.: 2 Cov.: 32 AF XY: 0.000210 AC XY: 152 AN XY: 724384

African (AFR) AF: 0.00871 AC: 291 AN: 33392

American (AMR) AF: 0.000852 AC: 38 AN: 44616

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 86046

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5548

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1109014

Other (OTH) AF: 0.000665 AC: 40 AN: 60180

GnomAD4 genome AF: 0.00270 AC: 411 AN: 152230 Hom.: 1 Cov.: 33 AF XY: 0.00251 AC XY: 187 AN XY: 74426

African (AFR) AF: 0.00888 AC: 369 AN: 41552

American (AMR) AF: 0.00190 AC: 29 AN: 15292

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68000

Other (OTH) AF: 0.00426 AC: 9 AN: 2112

Alfa AF: 0.00101 Hom.: 0

Bravo AF: 0.00289

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		6.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.96
dbscSNV1_RF	Benign	0.65
SpliceAI score (max)		0.040		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: rs145123059; hg19: chr11-47264270;