rs136485

Positions:

• chr22-32196133-T-A

Variant summary

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

The NM_001364983.3(RFPL2):​c.191A>T​(p.Asp64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,068 control chromosomes in the GnomAD database, including 25,423 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.55 (25423 hom., cov: 32)
• Consequence: RFPL2 NM_001364983.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RFPL2	NM_001394555.1	c.120-1643A>T		intron_variant		ENST00000652607.2	NP_001381484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RFPL2	ENST00000652607.2	c.120-1643A>T		intron_variant			NM_001394555.1	ENSP00000498332.1

Frequencies

GnomAD3 genomes AF: 0.548 AC: 83334 AN: 151950 Hom.: 25370 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.515

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

GnomAD4 genome AF: 0.549 AC: 83446 AN: 152068 Hom.: 25423 Cov.: 32 AF XY: 0.538 AC XY: 39967 AN XY: 74338

Gnomad4 AFR AF: 0.814

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.384

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.515

Alfa AF: 0.530 Hom.: 2850

Bravo AF: 0.561

Asia WGS AF: 0.354 AC: 1230 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	1.1
DANN	Benign	0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs136485; hg19: chr22-32592120;