rs136477

Positions:

• chr22-32192365-A-C

Variant summary

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

The NM_001394555.1(RFPL2):​c.556+537T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,016 control chromosomes in the GnomAD database, including 24,224 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 0.54 (24224 hom., cov: 32)
• Consequence: RFPL2 NM_001394555.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979

Genes affected

RFPL2 (HGNC:9979): (ret finger protein like 2) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be active in chromatin and nucleoplasm. [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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RFPL2	NM_001394555.1	c.556+537T>G		intron_variant		ENST00000652607.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RFPL2	ENST00000652607.2	c.556+537T>G		intron_variant			NM_001394555.1	P1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81748 AN: 151898 Hom.: 24176 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.538 AC: 81853 AN: 152016 Hom.: 24224 Cov.: 32 AF XY: 0.528 AC XY: 39238 AN XY: 74286

Gnomad4 AFR AF: 0.780

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.140

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.506

Alfa AF: 0.529 Hom.: 5641

Bravo AF: 0.550

Asia WGS AF: 0.352 AC: 1222 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.65

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: rs136477; hg19: chr22-32588352;