rs2272040

Positions:

• chr4-70141330-A-G

Variant summary

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

The ENST00000502441.2(PRR27):​n.98-62A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 400,876 control chromosomes in the GnomAD database, including 3,858 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 0.12 (1269 hom., cov: 32)
  • Exomes 𝑓: 0.14 (2589 hom.)
• Consequence: PRR27 ENST00000502441.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

Genes affected

PRR27 (HGNC:33193): (proline rich 27) Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CSN1S2BP (HGNC:20227): (casein alpha s2 like B, pseudogene) This locus is found in a cluster of casein genes, similar to other mammals. In human, the potential open reading frame that matches the homologous protein from other species is prematurely truncated shortly after the signal peptide. Therefore, this locus appears to be a pseudogene. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSN1S2BP	NR_033311.1	n.110-62A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRR27	ENST00000502441.2	n.98-62A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17673 AN: 151972 Hom.: 1268 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.0852

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.139 AC: 34459 AN: 248786 Hom.: 2589 AF XY: 0.140 AC XY: 20119 AN XY: 143768

Gnomad4 AFR exome AF: 0.0450

Gnomad4 AMR exome AF: 0.170

Gnomad4 ASJ exome AF: 0.213

Gnomad4 EAS exome AF: 0.197

Gnomad4 SAS exome AF: 0.143

Gnomad4 FIN exome AF: 0.0830

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.116 AC: 17678 AN: 152090 Hom.: 1269 Cov.: 32 AF XY: 0.116 AC XY: 8647 AN XY: 74348

Gnomad4 AFR AF: 0.0463

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.0852

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.166

Alfa AF: 0.133 Hom.: 648

Bravo AF: 0.122

Asia WGS AF: 0.140 AC: 485 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0090
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2272040; hg19: chr4-71007047;