dbSNP rs1449463226: RFPL4A:p.Lys66Glu (chr19-55761996-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001145014.2(RFPL4A):c.196A>G(p.Lys66Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 146,134 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 30)

Consequence

RFPL4A
NM_001145014.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.203

Publications

0 publications found

Variant links:

Genes affected

RFPL4A (HGNC:16449): (ret finger protein like 4A) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in nucleus. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05611348).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145014.2. 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
	RFPL4A	NM_001145014.2	MANE Select	c.196A>G	p.Lys66Glu	missense	Exon 2 of 3	NP_001138486.1	A6NLU0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL4A	ENST00000434937.3	TSL:5 MANE Select	c.196A>G	p.Lys66Glu	missense	Exon 2 of 3	ENSP00000392936.2	A6NLU0
	RFPL4A	ENST00000897443.1		c.196A>G	p.Lys66Glu	missense	Exon 1 of 2	ENSP00000567502.1

Frequencies

GnomAD3 genomes

AF:

0.00000684

AC:

AN:

146134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000262

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000684

AC:

AN:

146134

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

71310

show subpopulations

African (AFR)

AF:

0.0000262

AC:

AN:

38214

American (AMR)

AF:

0.00

AC:

AN:

14772

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4626

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66396

Other (OTH)

AF:

0.00

AC:

AN:

2000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.9

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.0067

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0090

LIST_S2

Benign

0.33

M_CAP

Benign

0.0027

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.5

PhyloP100

-0.20

PrimateAI

Uncertain

0.55

PROVEAN

Benign

0.20

REVEL

Benign

0.0070

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.016

Polyphen

0.098

Vest4

0.069

MutPred

0.46

Loss of MoRF binding (P = 0.0104)

MVP

0.040

MPC

1.4

ClinPred

0.097

GERP RS

1.1

Varity_R

0.098

gMVP

0.085

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over