rs9311109

chr3-35759275-T-Cchr3-35759275-T-G

Variant summary

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

The NM_001385562.1(ARPP21):c.2137+15310T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,100 control chromosomes in the GnomAD database, including 1,338 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 0.13 (1338 hom., cov: 32)
• Consequence: ARPP21 NM_001385562.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ARPP21	NM_001385562.1	c.2137+15310T>C		intron_variant		ENST00000684406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ARPP21	ENST00000684406.1	c.2137+15310T>C		intron_variant			NM_001385562.1	P4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19244 AN: 151982 Hom.: 1334 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19264 AN: 152100 Hom.: 1338 Cov.: 32 AF XY: 0.120 AC XY: 8950 AN XY: 74352

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.0954

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.153

Gnomad4 OTH AF: 0.137

Alfa AF: 0.131 Hom.: 284

Bravo AF: 0.128

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.0
Dann	Benign	0.56

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: rs9311109; hg19: chr3-35800767;