rs2071484

Variant names:

• chr19-11577645-T-C
• rs2071484
• ENST00000218758.10:c.-53A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000218758.10(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 ENST00000218758.10 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.04
• Publications: 28 publications found

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]

LOC124904638 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
ACP5	NM_001611.5	c.-53A>G		5_prime_UTR_variant	Exon 1 of 5	ENST00000648477.1	NP_001602.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACP5	ENST00000648477.1	c.-53A>G		5_prime_UTR_variant	Exon 1 of 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

African (AFR) AF: 0.640 AC: 6108 AN: 9538

American (AMR) AF: 0.435 AC: 6324 AN: 14554

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 4508 AN: 9686

East Asian (EAS) AF: 0.507 AC: 9843 AN: 19426

South Asian (SAS) AF: 0.432 AC: 18519 AN: 42900

European-Finnish (FIN) AF: 0.285 AC: 4930 AN: 17298

Middle Eastern (MID) AF: 0.480 AC: 664 AN: 1382

European-Non Finnish (NFE) AF: 0.341 AC: 64166 AN: 187972

Other (OTH) AF: 0.393 AC: 7192 AN: 18290

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

African (AFR) AF: 0.640 AC: 26574 AN: 41508

American (AMR) AF: 0.427 AC: 6522 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1632 AN: 3470

East Asian (EAS) AF: 0.542 AC: 2798 AN: 5162

South Asian (SAS) AF: 0.443 AC: 2138 AN: 4826

European-Finnish (FIN) AF: 0.286 AC: 3028 AN: 10594

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22872 AN: 67952

Other (OTH) AF: 0.461 AC: 973 AN: 2112

Alfa AF: 0.390 Hom.: 38675

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		1.0
PromoterAI		0.097	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2071484; hg19: chr19-11688460;