Genetic Variant NM_004300.4:c.43+8G>A (chr2-265015-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004300.4(ACP1):c.43+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00157 in 1,612,678 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00091 ( 18 hom. )

Consequence

ACP1
NM_004300.4 splice_region, intron

Scores

Splicing: ADA: 0.0001409

Clinical Significance

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

Conservation

PhyloP100: -0.155

Publications

2 publications found

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:

SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3YL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 2-265015-G-A is Benign according to our data. Variant chr2-265015-G-A is described in ClinVar as Benign. ClinVar VariationId is 788388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00783 (1193/152348) while in subpopulation AFR AF = 0.0269 (1120/41592). AF 95% confidence interval is 0.0256. There are 10 homozygotes in GnomAd4. There are 570 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004300.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACP1	NM_004300.4	MANE Select	c.43+8G>A	splice_region intron	N/A	NP_004291.1	P24666-1
ACP1	NM_007099.4		c.43+8G>A	splice_region intron	N/A	NP_009030.1	P24666-2
ACP1	NM_001040649.3		c.43+8G>A	splice_region intron	N/A	NP_001035739.1	A0A140VK37

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACP1	ENST00000272065.10	TSL:1 MANE Select	c.43+8G>A	splice_region intron	N/A	ENSP00000272065.5	P24666-1
ACP1	ENST00000272067.11	TSL:1	c.43+8G>A	splice_region intron	N/A	ENSP00000272067.6	P24666-2
ACP1	ENST00000407983.7	TSL:1	c.43+8G>A	splice_region intron	N/A	ENSP00000385404.3	P24666-4

Frequencies

GnomAD3 genomes

AF:

0.00778

AC:

1185

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0268

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00294

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00207

AC:

511

AN:

247196

AF XY:

0.00149

show subpopulations

Gnomad AFR exome

AF:

0.0277

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000807

Gnomad OTH exome

AF:

0.00133

GnomAD4 exome

AF:

0.000912

AC:

1332

AN:

1460330

Hom.:

Cov.:

AF XY:

0.000761

AC XY:

553

AN XY:

726530

show subpopulations

African (AFR)

AF:

0.0304

AC:

1008

AN:

33166

American (AMR)

AF:

0.00184

AC:

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26066

East Asian (EAS)

AF:

0.00

AC:

AN:

39564

South Asian (SAS)

AF:

0.000116

AC:

AN:

86050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000675

AC:

AN:

1111398

Other (OTH)

AF:

0.00232

AC:

140

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

126

190

253

316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00783

AC:

1193

AN:

152348

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

570

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0269

AC:

1120

AN:

41592

American (AMR)

AF:

0.00294

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000132

AC:

AN:

68034

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

127

191

254

318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00439

Hom.:

Bravo

AF:

0.00928

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.4

(source)

DANN

Benign

0.96

PhyloP100

-0.15

PromoterAI

-0.046

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00014

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over