rs136485

Variant names:

• chr22-32196133-T-A
• rs136485
• NM_001394555.1:c.120-1643A>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364983.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL2	NM_001394555.1	MANE Select	c.120-1643A>T		intron	N/A	NP_001381484.1	O75678-1
	RFPL2	NM_001364983.3		c.191A>T	p.Asp64Val	missense	Exon 3 of 6	NP_001351912.1
	RFPL2	NM_001364986.3		c.191A>T	p.Asp64Val	missense	Exon 3 of 6	NP_001351915.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL2	ENST00000652607.2	MANE Select	c.120-1643A>T		intron	N/A	ENSP00000498332.1	O75678-1
	RFPL2	ENST00000628378.1	TSL:1	n.120-1735A>T		intron	N/A	ENSP00000487290.1	A0A0D9SGA4
	RFPL2	ENST00000248983.8	TSL:5	c.120-1643A>T		intron	N/A	ENSP00000248983.5	O75678-1

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

African (AFR) AF: 0.814 AC: 33731 AN: 41464

American (AMR) AF: 0.431 AC: 6583 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3470

East Asian (EAS) AF: 0.141 AC: 729 AN: 5182

South Asian (SAS) AF: 0.381 AC: 1839 AN: 4824

European-Finnish (FIN) AF: 0.384 AC: 4051 AN: 10558

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33094 AN: 67980

Other (OTH) AF: 0.515 AC: 1085 AN: 2106

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.15
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs136485; hg19: chr22-32592120;