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GeneBe

11-47240140-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001610.4(ACP2):c.1248C>T(p.Val416=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,613,984 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 18 hom., cov: 32)
Exomes 𝑓: 0.00075 ( 12 hom. )

Consequence

ACP2
NM_001610.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.34
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 11-47240140-G-A is Benign according to our data. Variant chr11-47240140-G-A is described in ClinVar as [Benign]. Clinvar id is 776606.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.34 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00773 (1178/152346) while in subpopulation AFR AF= 0.0262 (1091/41578). AF 95% confidence interval is 0.0249. There are 18 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ACP2NM_001610.4 linkuse as main transcriptc.1248C>T p.Val416= synonymous_variant 11/11 ENST00000672073.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ACP2ENST00000672073.1 linkuse as main transcriptc.1248C>T p.Val416= synonymous_variant 11/11 NM_001610.4 P1P11117-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00775
AC:
1180
AN:
152228
Hom.:
18
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0263
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00573
GnomAD3 exomes
AF:
0.00200
AC:
501
AN:
250748
Hom.:
4
AF XY:
0.00153
AC XY:
207
AN XY:
135604
show subpopulations
Gnomad AFR exome
AF:
0.0265
Gnomad AMR exome
AF:
0.00153
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000971
Gnomad OTH exome
AF:
0.00115
GnomAD4 exome
AF:
0.000748
AC:
1093
AN:
1461638
Hom.:
12
Cov.:
31
AF XY:
0.000693
AC XY:
504
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.0247
Gnomad4 AMR exome
AF:
0.00174
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.00174
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00773
AC:
1178
AN:
152346
Hom.:
18
Cov.:
32
AF XY:
0.00738
AC XY:
550
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.0262
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.00567
Alfa
AF:
0.00398
Hom.:
1
Bravo
AF:
0.00893
Asia WGS
AF:
0.00260
AC:
9
AN:
3478
EpiCase
AF:
0.000218
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeMar 30, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
Cadd
Benign
3.3
Dann
Benign
0.79

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2228401; hg19: chr11-47261691; API