rs2071484

Positions:

• chr19-11577645-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001111034.3(ACP5):​c.-53A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 473,148 control chromosomes in the GnomAD database, including 40,517 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (16203 hom., cov: 32)
  • Exomes 𝑓: 0.38 (24314 hom.)
• Consequence: ACP5 NM_001111034.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04

Genes affected

ACP5 (HGNC:124): (acid phosphatase 5, tartrate resistant) This gene encodes an iron containing glycoprotein which catalyzes the conversion of orthophosphoric monoester to alcohol and orthophosphate. It is the most basic of the acid phosphatases and is the only form not inhibited by L(+)-tartrate. [provided by RefSeq, Aug 2008]

ZNF627 (HGNC:30570): (zinc finger protein 627) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACP5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 19-11577645-T-C is Benign according to our data. Variant chr19-11577645-T-C is described in ClinVar as [Benign]. Clinvar id is 1234961.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP5	NM_001611.5	c.-53A>G		5_prime_UTR_variant	1/5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1	c.-53A>G		5_prime_UTR_variant	1/5		NM_001611.5	ENSP00000496973.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66909 AN: 151984 Hom.: 16166 Cov.: 32

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.542

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.381 AC: 122254 AN: 321046 Hom.: 24314 Cov.: 0 AF XY: 0.383 AC XY: 65022 AN XY: 169684

Gnomad4 AFR exome AF: 0.640

Gnomad4 AMR exome AF: 0.435

Gnomad4 ASJ exome AF: 0.465

Gnomad4 EAS exome AF: 0.507

Gnomad4 SAS exome AF: 0.432

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.440 AC: 66996 AN: 152102 Hom.: 16203 Cov.: 32 AF XY: 0.439 AC XY: 32669 AN XY: 74354

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.542

Gnomad4 SAS AF: 0.443

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.461

Alfa AF: 0.374 Hom.: 19913

Bravo AF: 0.461

Asia WGS AF: 0.526 AC: 1830 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs2071484; hg19: chr19-11688460;