rs136477

Variant names:

• chr22-32192365-A-C
• rs136477
• NM_001394555.1:c.556+537T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RFPL2	NM_001394555.1	c.556+537T>G		intron_variant	Intron 4 of 4	ENST00000652607.2	NP_001381484.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RFPL2	ENST00000652607.2	c.556+537T>G		intron_variant	Intron 4 of 4		NM_001394555.1	ENSP00000498332.1

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

African (AFR) AF: 0.780 AC: 32318 AN: 41458

American (AMR) AF: 0.426 AC: 6503 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1749 AN: 3470

East Asian (EAS) AF: 0.140 AC: 724 AN: 5166

South Asian (SAS) AF: 0.382 AC: 1837 AN: 4810

European-Finnish (FIN) AF: 0.385 AC: 4063 AN: 10550

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33004 AN: 67972

Other (OTH) AF: 0.506 AC: 1070 AN: 2114

Alfa AF: 0.512 Hom.: 9004

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
PhyloP100		-0.98
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs136477; hg19: chr22-32588352; COSMIC: COSV107217918; COSMIC: COSV107217918;