Variant 21-43687681-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015056.3(RRP1B):c.1307T>A(p.Leu436Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L436V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RRP1B
NM_015056.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.116

Variant links:

Genes affected

RRP1B (HGNC:23818): (ribosomal RNA processing 1B) Enables transcription coactivator activity. Involved in several processes, including cellular response to virus; positive regulation by host of viral transcription; and positive regulation of transcription by RNA polymerase II. Located in chromosome; granular component; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RRP1B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040130347).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RRP1B	NM_015056.3 linkuse as main transcript	c.1307T>A	p.Leu436Gln	missense_variant	13/16	ENST00000340648.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RRP1B	ENST00000340648.6 linkuse as main transcript	c.1307T>A	p.Leu436Gln	missense_variant	13/16	1	NM_015056.3	P1	Q14684-1
RRP1B	ENST00000470886.1 linkuse as main transcript	n.970T>A		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1451184

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720532

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.23

DANN

Benign

0.16

DEOGEN2

Benign

0.0077

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.18

M_CAP

Benign

0.0076

MetaRNN

Benign

0.040

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

1.1

REVEL

Benign

0.018

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.052

MutPred

0.25

Gain of solvent accessibility (P = 0.0374);

MVP

0.18

MPC

0.35

ClinPred

0.036

GERP RS

-3.2

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

2.1

Varity_R

0.089

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over