chr19-50790698-G-A

Variant names:

• chr19-50790698-G-A
• rs2162784
• NM_033068.3:c.216G>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 2P and 9B. PP3_Moderate BP6 BA1

The NM_033068.3(ACP4):​c.216G>A​(p.Thr72Thr) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.0887 in 1,545,498 control chromosomes in the GnomAD database, including 6,439 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.10 (842 hom., cov: 31)
  • Exomes 𝑓: 0.087 (5597 hom.)
• Consequence: ACP4 NM_033068.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.9999
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 4.78
• Publications: 10 publications found

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]

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

LOC105372439 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. Scorers claiming Uncertain: max_spliceai. No scorers claiming Benign.
• BP6: Variant 19-50790698-G-A is Benign according to our data. Variant chr19-50790698-G-A is described in ClinVar as [Benign]. Clinvar id is 3058974.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP4	NM_033068.3	c.216G>A	p.Thr72Thr	splice_region_variant, synonymous_variant	Exon 2 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3	n.435-983C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP4	ENST00000270593.2	c.216G>A	p.Thr72Thr	splice_region_variant, synonymous_variant	Exon 2 of 11	1	NM_033068.3	ENSP00000270593.1
SMIM47	ENST00000636757.1	c.-59-983C>T		intron_variant	Intron 2 of 4	5		ENSP00000489695.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15486 AN: 151722 Hom.: 845 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.0797

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0466

Gnomad FIN AF: 0.0972

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.0898

Gnomad OTH AF: 0.112

GnomAD2 exomes AF: 0.0874 AC: 12707 AN: 145348 AF XY: 0.0860

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0568

Gnomad ASJ exome AF: 0.154

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.0971

Gnomad NFE exome AF: 0.0902

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0872 AC: 121596 AN: 1393658 Hom.: 5597 Cov.: 40 AF XY: 0.0865 AC XY: 59485 AN XY: 687656

African (AFR) AF: 0.136 AC: 4316 AN: 31702

American (AMR) AF: 0.0596 AC: 2138 AN: 35846

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 3866 AN: 25140

East Asian (EAS) AF: 0.120 AC: 4296 AN: 35890

South Asian (SAS) AF: 0.0473 AC: 3749 AN: 79214

European-Finnish (FIN) AF: 0.0910 AC: 4017 AN: 44142

Middle Eastern (MID) AF: 0.126 AC: 626 AN: 4970

European-Non Finnish (NFE) AF: 0.0861 AC: 92902 AN: 1078902

Other (OTH) AF: 0.0983 AC: 5686 AN: 57852

GnomAD4 genome AF: 0.102 AC: 15480 AN: 151840 Hom.: 842 Cov.: 31 AF XY: 0.102 AC XY: 7586 AN XY: 74230

African (AFR) AF: 0.130 AC: 5375 AN: 41410

American (AMR) AF: 0.0795 AC: 1215 AN: 15280

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

East Asian (EAS) AF: 0.120 AC: 612 AN: 5118

South Asian (SAS) AF: 0.0460 AC: 221 AN: 4808

European-Finnish (FIN) AF: 0.0972 AC: 1028 AN: 10578

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.0898 AC: 6094 AN: 67870

Other (OTH) AF: 0.110 AC: 233 AN: 2110

Alfa AF: 0.0989 Hom.: 223

Bravo AF: 0.105

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ACP4-related disorder Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Benign	0.95
PhyloP100		4.8
PromoterAI		-0.022	Neutral
Mutation Taster		=19/81	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	1.0
SpliceAI score (max)		0.42		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.42		Position offset: 11
DS_DL_spliceai		0.31		Position offset: 0

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

Other links and lift over

dbSNP: rs2162784; hg19: chr19-51293955; COSMIC: COSV54516866; COSMIC: COSV54516866;