19-50790456-CCTG-C

Variant names:

• chr19-50790456-CCTG-C
• rs750637211
• NM_033068.3:c.58_60delCTG

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_033068.3(ACP4):​c.58_60delCTG​(p.Leu20del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00223 in 1,523,522 control chromosomes in the GnomAD database, including 31 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0074 (19 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (12 hom.)
• Consequence: ACP4 NM_033068.3 conservative_inframe_deletion
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.16
• Publications: 2 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 -9 ACMG points.

• BP6: Variant 19-50790456-CCTG-C is Benign according to our data. Variant chr19-50790456-CCTG-C is described in ClinVar as [Benign]. Clinvar id is 3059630.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00737 (1119/151886) while in subpopulation AFR AF = 0.026 (1079/41470). AF 95% confidence interval is 0.0247. There are 19 homozygotes in GnomAd4. There are 508 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1119 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACP4	NM_033068.3	c.58_60delCTG	p.Leu20del	conservative_inframe_deletion	Exon 1 of 11	ENST00000270593.2	NP_149059.1
LOC105372439	XR_936026.3	n.435-744_435-742delCAG		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP4	ENST00000270593.2	c.58_60delCTG	p.Leu20del	conservative_inframe_deletion	Exon 1 of 11	1	NM_033068.3	ENSP00000270593.1
SMIM47	ENST00000636757.1	c.-59-744_-59-742delCAG		intron_variant	Intron 2 of 4	5		ENSP00000489695.1

Frequencies

GnomAD3 genomes AF: 0.00737 AC: 1119 AN: 151772 Hom.: 19 Cov.: 32

Gnomad AFR AF: 0.0261

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00719 AC: 1083 AN: 150628 AF XY: 0.00689

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.00417

Gnomad ASJ exome AF: 0.00782

Gnomad EAS exome AF: 0.00272

Gnomad FIN exome AF: 0.00799

Gnomad NFE exome AF: 0.00607

Gnomad OTH exome AF: 0.00487

GnomAD4 exome AF: 0.00166 AC: 2282 AN: 1371636 Hom.: 12 AF XY: 0.00176 AC XY: 1195 AN XY: 677936

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0302 AC: 953 AN: 31606

American (AMR) AF: 0.00335 AC: 124 AN: 37018

Ashkenazi Jewish (ASJ) AF: 0.00225 AC: 54 AN: 23954

East Asian (EAS) AF: 0.000737 AC: 27 AN: 36618

South Asian (SAS) AF: 0.00197 AC: 148 AN: 75094

European-Finnish (FIN) AF: 0.00256 AC: 114 AN: 44560

Middle Eastern (MID) AF: 0.000444 AC: 2 AN: 4502

European-Non Finnish (NFE) AF: 0.000673 AC: 715 AN: 1061642

Other (OTH) AF: 0.00256 AC: 145 AN: 56642

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00737 AC: 1119 AN: 151886 Hom.: 19 Cov.: 32 AF XY: 0.00684 AC XY: 508 AN XY: 74224

African (AFR) AF: 0.0260 AC: 1079 AN: 41470

American (AMR) AF: 0.00157 AC: 24 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10512

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

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67854

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.0248 Hom.: 0

Bravo AF: 0.00835

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ACP4-related disorder Benign:1

Aug 15, 2019

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
PhyloP100		2.2
Mutation Taster		=85/15	polymorphism

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

Other links and lift over

dbSNP: rs750637211; hg19: chr19-51293713; COSMIC: COSV104374403; COSMIC: COSV104374403;