rs2305234

Positions:

• chr3-35744116-G-A

Variant summary

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

The NM_001385562.1(ARPP21):​c.2137+151G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 794,540 control chromosomes in the GnomAD database, including 4,721 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 (831 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3890 hom.)
• Consequence: ARPP21 NM_001385562.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.251

Genes affected

ARPP21 (HGNC:16968): (cAMP regulated phosphoprotein 21) This gene encodes a cAMP-regulated phosphoprotein. The encoded protein is enriched in the caudate nucleus and cerebellar cortex. A similar protein in mouse may be involved in regulating the effects of dopamine in the basal ganglia. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jun 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ARPP21	NM_001385562.1	c.2137+151G>A		intron_variant		ENST00000684406.1	NP_001372491.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ARPP21	ENST00000684406.1	c.2137+151G>A		intron_variant			NM_001385562.1	ENSP00000506922	P4

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15460 AN: 152128 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0966

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.0673

Gnomad FIN AF: 0.0867

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0761

GnomAD4 exome AF: 0.103 AC: 66126 AN: 642294 Hom.: 3890 AF XY: 0.102 AC XY: 34181 AN XY: 333864

Gnomad4 AFR exome AF: 0.0793

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.127

Gnomad4 EAS exome AF: 0.0581

Gnomad4 SAS exome AF: 0.0697

Gnomad4 FIN exome AF: 0.0854

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.0990

GnomAD4 genome AF: 0.102 AC: 15459 AN: 152246 Hom.: 831 Cov.: 32 AF XY: 0.0989 AC XY: 7361 AN XY: 74446

Gnomad4 AFR AF: 0.0832

Gnomad4 AMR AF: 0.0964

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0691

Gnomad4 SAS AF: 0.0667

Gnomad4 FIN AF: 0.0867

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.0754

Alfa AF: 0.112 Hom.: 1000

Bravo AF: 0.102

Asia WGS AF: 0.0810 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.1
DANN	Benign	0.80

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: rs2305234; hg19: chr3-35785608;