2-265017-C-T

Variant names:

• chr2-265017-C-T
• rs143584646
• NM_004300.4:c.43+10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004300.4(ACP1):​c.43+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00127 in 1,612,380 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0064 (12 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (8 hom.)
• Consequence: ACP1 NM_004300.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.951
• Publications: 0 publications found

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-265017-C-T is Benign according to our data. Variant chr2-265017-C-T is described in ClinVar as Benign. ClinVar VariationId is 712259.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 = 0.00636 (968/152318) while in subpopulation AFR AF = 0.0217 (904/41580). AF 95% confidence interval is 0.0206. There are 12 homozygotes in GnomAd4. There are 453 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACP1	NM_004300.4	MANE Select	c.43+10C>T		intron	N/A	NP_004291.1	P24666-1
	ACP1	NM_007099.4		c.43+10C>T		intron	N/A	NP_009030.1	P24666-2
	ACP1	NM_001040649.3		c.43+10C>T		intron	N/A	NP_001035739.1	A0A140VK37

Ensembl Transcripts

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

Frequencies

GnomAD3 genomes AF: 0.00633 AC: 963 AN: 152200 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.0216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00173 AC: 428 AN: 247478 AF XY: 0.00136

Gnomad AFR exome AF: 0.0222

Gnomad AMR exome AF: 0.00117

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00138

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.00133

GnomAD4 exome AF: 0.000742 AC: 1083 AN: 1460062 Hom.: 8 Cov.: 31 AF XY: 0.000692 AC XY: 503 AN XY: 726380

African (AFR) AF: 0.0228 AC: 754 AN: 33122

American (AMR) AF: 0.00164 AC: 73 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26052

East Asian (EAS) AF: 0.000582 AC: 23 AN: 39542

South Asian (SAS) AF: 0.0000581 AC: 5 AN: 86034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5758

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111278

Other (OTH) AF: 0.00232 AC: 140 AN: 60300

GnomAD4 genome AF: 0.00636 AC: 968 AN: 152318 Hom.: 12 Cov.: 33 AF XY: 0.00608 AC XY: 453 AN XY: 74472

African (AFR) AF: 0.0217 AC: 904 AN: 41580

American (AMR) AF: 0.00242 AC: 37 AN: 15312

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

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68022

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

Alfa AF: 0.00365 Hom.: 4

Bravo AF: 0.00696

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.6
DANN	Benign	0.96
PhyloP100		-0.95
PromoterAI		-0.034	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs143584646; hg19: chr2-265017;