rs2297988

chr10-97358625-T-C

Variant summary

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

The NM_015179.4(RRP12):c.3709-6A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 1,606,020 control chromosomes in the GnomAD database, including 95,121 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.40 (13108 hom., cov: 30)
  • Exomes 𝑓: 0.33 (82013 hom.)
• Consequence: RRP12 NM_015179.4 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.000008779
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227

Genes affected

RRP12 (HGNC:29100): (ribosomal RNA processing 12 homolog) Enables RNA binding activity. Predicted to be involved in rRNA processing. Located in cytosol; nucleolus; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP12	NM_015179.4	c.3709-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000370992.9
RRP12	NM_001145114.1	c.3526-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
RRP12	NM_001284337.2	c.3409-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
RRP12	XM_047424903.1	c.3625-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP12	ENST00000370992.9	c.3709-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015179.4	P1

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60721 AN: 151636 Hom.: 13076 Cov.: 30

Gnomad AFR AF: 0.568

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.370

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.342 AC: 85847 AN: 251342 Hom.: 15365 AF XY: 0.340 AC XY: 46247 AN XY: 135838

Gnomad AFR exome AF: 0.573

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.362

Gnomad EAS exome AF: 0.298

Gnomad SAS exome AF: 0.353

Gnomad FIN exome AF: 0.350

Gnomad NFE exome AF: 0.321

Gnomad OTH exome AF: 0.347

GnomAD4 exome AF: 0.331 AC: 481150 AN: 1454264 Hom.: 82013 Cov.: 31 AF XY: 0.331 AC XY: 239900 AN XY: 723774

Gnomad4 AFR exome AF: 0.580

Gnomad4 AMR exome AF: 0.309

Gnomad4 ASJ exome AF: 0.365

Gnomad4 EAS exome AF: 0.286

Gnomad4 SAS exome AF: 0.353

Gnomad4 FIN exome AF: 0.351

Gnomad4 NFE exome AF: 0.321

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.401 AC: 60809 AN: 151756 Hom.: 13108 Cov.: 30 AF XY: 0.402 AC XY: 29796 AN XY: 74166

Gnomad4 AFR AF: 0.569

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.389

Alfa AF: 0.346 Hom.: 7715

Bravo AF: 0.406

Asia WGS AF: 0.364 AC: 1269 AN: 3478

EpiCase AF: 0.326

EpiControl AF: 0.326

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	4.2
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000088
SpliceAI score (max)		0.090		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: rs2297988; hg19: chr10-99118382; COSMIC: COSV59668229;