chr2-265015-G-A

Position:

• chr2-265015-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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

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

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACP1	NM_004300.4	c.43+8G>A		splice_region_variant, intron_variant		ENST00000272065.10	NP_004291.1
ACP1	NM_001040649.3	c.43+8G>A		splice_region_variant, intron_variant			NP_001035739.1
ACP1	NM_007099.4	c.43+8G>A		splice_region_variant, intron_variant			NP_009030.1
ACP1	NR_024080.2	n.61+8G>A		splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACP1	ENST00000272065.10	c.43+8G>A		splice_region_variant, intron_variant		1	NM_004300.4	ENSP00000272065	P3

Frequencies

GnomAD3 genomes AF: 0.00778 AC: 1185 AN: 152230 Hom.: 10 Cov.: 33

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

GnomAD3 exomes AF: 0.00207 AC: 511 AN: 247196 Hom.: 3 AF XY: 0.00149 AC XY: 199 AN XY: 133992

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 SAS exome AF: 0.000198

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.: 18 Cov.: 31 AF XY: 0.000761 AC XY: 553 AN XY: 726530

Gnomad4 AFR exome AF: 0.0304

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000675

Gnomad4 OTH exome AF: 0.00232

GnomAD4 genome AF: 0.00783 AC: 1193 AN: 152348 Hom.: 10 Cov.: 33 AF XY: 0.00765 AC XY: 570 AN XY: 74498

Gnomad4 AFR AF: 0.0269

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00415 Hom.: 5

Bravo AF: 0.00928

Asia WGS AF: 0.00173 AC: 6 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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
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	-0.68
CADD	Benign	2.4
DANN	Benign	0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs116051772; hg19: chr2-265015;