chr21-43687681-T-G

Variant names:

• chr21-43687681-T-G
• rs9306160
• NM_015056.3:c.1307T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015056.3(RRP1B):​c.1307T>G​(p.Leu436Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,451,184 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.0000014 (0 hom.)
• Consequence: RRP1B NM_015056.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

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]

ACMG classification

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=0.03719467).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015056.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1B	NM_015056.3	MANE Select	c.1307T>G	p.Leu436Arg	missense	Exon 13 of 16	NP_055871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1B	ENST00000340648.6	TSL:1 MANE Select	c.1307T>G	p.Leu436Arg	missense	Exon 13 of 16	ENSP00000339145.4
	RRP1B	ENST00000470886.1	TSL:2	n.970T>G		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451184 Hom.: 0 Cov.: 60 AF XY: 0.00 AC XY: 0 AN XY: 720532

African (AFR) AF: 0.00 AC: 0 AN: 33132

American (AMR) AF: 0.00 AC: 0 AN: 44044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25694

East Asian (EAS) AF: 0.00 AC: 0 AN: 39534

South Asian (SAS) AF: 0.00 AC: 0 AN: 85794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1105456

Other (OTH) AF: 0.00 AC: 0 AN: 59804

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.12
DANN	Benign	0.31
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00049	N
LIST_S2	Benign	0.17	T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.5	N
PhyloP100		-0.12
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.9	N
REVEL	Benign	0.033
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.035
MutPred		0.34		Gain of methylation at L436 (P = 0.0166)
MVP		0.19
MPC		0.50
ClinPred		0.039	T
GERP RS		-3.2
Varity_R		0.10
gMVP		0.10
Mutation Taster		=97/3	polymorphism

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: rs9306160; hg19: chr21-45107562;