rs1055746

Positions:

• chr15-52551073-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006628.6(ARPP19):​c.*861T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,688 control chromosomes in the GnomAD database, including 887 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (886 hom., cov: 33)
  • Exomes 𝑓: 0.060 (1 hom.)
• Consequence: ARPP19 NM_006628.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

Genes affected

ARPP19 (HGNC:16967): (cAMP regulated phosphoprotein 19) The 19-kD cAMP-regulated phosphoprotein plays a role in regulating mitosis by inhibiting protein phosphatase-2A (PP2A; see MIM 176915) (summary by Gharbi-Ayachi et al., 2010 [PubMed 21164014]).[supplied by OMIM, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPP19	NM_006628.6	c.*861T>G		3_prime_UTR_variant	3/3	ENST00000249822.9	NP_006619.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPP19	ENST00000249822.9	c.*861T>G		3_prime_UTR_variant	3/3	1	NM_006628.6	ENSP00000249822	P1
ARPP19	ENST00000566423.5	c.*861T>G		3_prime_UTR_variant	4/4	1		ENSP00000455625	P1
ARPP19	ENST00000561650.5	c.*861T>G		3_prime_UTR_variant	3/3	2		ENSP00000454234

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15610 AN: 152140 Hom.: 887 Cov.: 33

Gnomad AFR AF: 0.0888

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.0521

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.0605 AC: 26 AN: 430 Hom.: 1 Cov.: 0 AF XY: 0.0577 AC XY: 15 AN XY: 260

Gnomad4 FIN exome AF: 0.0590

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.102 AC: 15601 AN: 152258 Hom.: 886 Cov.: 33 AF XY: 0.0971 AC XY: 7233 AN XY: 74460

Gnomad4 AFR AF: 0.0886

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0847

Gnomad4 FIN AF: 0.0521

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.125

Alfa AF: 0.118 Hom.: 410

Bravo AF: 0.107

Asia WGS AF: 0.0390 AC: 137 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.9
DANN	Benign	0.85

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

Other links and lift over

dbSNP: rs1055746; hg19: chr15-52843270;