Genetic Variant ACP4:p.Pro125Pro (chr19-50791727-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_033068.3(ACP4):c.375C>T(p.Pro125Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 1,613,146 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 60 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 50 hom. )

Consequence

ACP4
NM_033068.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.32

Publications

1 publications found

Variant links:

Genes affected

ACP4 (HGNC:14376): (acid phosphatase 4) Acid phosphatases are enzymes capable of hydrolyzing orthophosphoric acid esters in an acid medium. This gene is up-regulated by androgens and is down-regulated by estrogens in the prostate cancer cell line. This gene exhibits a lower level of expression in testicular cancer tissues than in normal tissues. The protein encoded by this gene has structural similarity to prostatic and lysosomal acid phosphatases. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

ACP4 links:

SMIM47 (HGNC:53452): (small integral membrane protein 47)

SMIM47 links:

LOC105372439 (HGNC:):

LOC105372439 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 19-50791727-C-T is Benign according to our data. Variant chr19-50791727-C-T is described in ClinVar as Benign. ClinVar VariationId is 777505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.32 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0133 (2021/152324) while in subpopulation AFR AF = 0.0455 (1893/41560). AF 95% confidence interval is 0.0438. There are 60 homozygotes in GnomAd4. There are 922 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 2021 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033068.3. 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
	ACP4	NM_033068.3	MANE Select	c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 11	NP_149059.1	Q9BZG2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP4	ENST00000270593.2	TSL:1 MANE Select	c.375C>T	p.Pro125Pro	synonymous	Exon 4 of 11	ENSP00000270593.1	Q9BZG2-1
	SMIM47	ENST00000636757.1	TSL:5	c.-60+678G>A		intron	N/A	ENSP00000489695.1	A0A1B0GTG8

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2019

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00341

AC:

851

AN:

249784

AF XY:

0.00239

show subpopulations

Gnomad AFR exome

AF:

0.0483

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000711

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.00137

AC:

2000

AN:

1460822

Hom.:

Cov.:

AF XY:

0.00114

AC XY:

828

AN XY:

726716

show subpopulations

African (AFR)

AF:

0.0503

AC:

1685

AN:

33474

American (AMR)

AF:

0.00221

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26114

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39690

South Asian (SAS)

AF:

0.000209

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52598

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1111854

Other (OTH)

AF:

0.00285

AC:

172

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

122

244

367

489

611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0133

AC:

2021

AN:

152324

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

922

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0455

AC:

1893

AN:

41560

American (AMR)

AF:

0.00634

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68034

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

197

296

394

493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00567

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0090

(source)

DANN

Benign

0.90

PhyloP100

-2.3

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over