Variant chr2-277229-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004300.4(ACP1):c.402G>A(p.Gly134=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 1,614,026 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0073 ( 63 hom. )

Consequence

ACP1
NM_004300.4 splice_region, synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.187

Variant links:

Genes affected

ACP1 (HGNC:122): (acid phosphatase 1) The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phosphatase and a protein tyrosine phosphatase by hydrolyzing protein tyrosine phosphate to protein tyrosine and orthophosphate. This enzyme also hydrolyzes orthophosphoric monoesters to alcohol and orthophosphate. This gene is genetically polymorphic, and three common alleles segregating at the corresponding locus give rise to six phenotypes. Each allele appears to encode at least two electrophoretically different isozymes, Bf and Bs, which are produced in allele-specific ratios. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Aug 2008]

ACP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 2-277229-G-A is Benign according to our data. Variant chr2-277229-G-A is described in ClinVar as [Benign]. Clinvar id is 712497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.187 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ACP1	NM_004300.4 linkuse as main transcript	c.402G>A	p.Gly134=	splice_region_variant, synonymous_variant	6/6	ENST00000272065.10
ACP1	NM_007099.4 linkuse as main transcript	c.402G>A	p.Gly134=	splice_region_variant, synonymous_variant	6/6
ACP1	NR_024080.2 linkuse as main transcript	n.449G>A		splice_region_variant, non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACP1	ENST00000272065.10 linkuse as main transcript	c.402G>A	p.Gly134=	splice_region_variant, synonymous_variant	6/6	1	NM_004300.4	P3	P24666-1

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

771

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.0173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00227

Gnomad FIN

AF:

0.000848

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00808

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00542

AC:

1363

AN:

251246

Hom.:

AF XY:

0.00565

AC XY:

768

AN XY:

135830

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00786

Gnomad OTH exome

AF:

0.00554

GnomAD4 exome

AF:

0.00726

AC:

10607

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

5277

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00423

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.00828

Gnomad4 OTH exome

AF:

0.00614

GnomAD4 genome

AF:

0.00506

AC:

771

AN:

152302

Hom.:

Cov.:

AF XY:

0.00489

AC XY:

364

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.0173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.000848

Gnomad4 NFE

AF:

0.00808

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00700

Hom.:

Bravo

AF:

0.00515

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00758

EpiControl

AF:

0.0101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 04, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.3

DANN

Benign

0.84

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over