Variant 21-43674628-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015056.3(RRP1B):c.358-8T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00183 in 1,490,314 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 25 hom., cov: 25)

Exomes 𝑓: 0.0010 ( 22 hom. )

Consequence

RRP1B
NM_015056.3 splice_region, intron

Scores

Splicing: ADA: 0.0001752

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.939

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 21-43674628-T-A is Benign according to our data. Variant chr21-43674628-T-A is described in ClinVar as [Benign]. Clinvar id is 773092.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00949 (1339/141088) while in subpopulation AFR AF= 0.0319 (1225/38452). AF 95% confidence interval is 0.0304. There are 25 homozygotes in gnomad4. There are 631 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RRP1B	NM_015056.3 link	c.358-8T>A		splice_region_variant, intron_variant		ENST00000340648.6	NP_055871.1	Q14684-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RRP1B	ENST00000340648.6 link	c.358-8T>A		splice_region_variant, intron_variant		1	NM_015056.3	ENSP00000339145.4		Q14684-1

Frequencies

GnomAD3 genomes

AF:

0.00946

AC:

1333

AN:

140982

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00579

Gnomad ASJ

AF:

0.000297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000709

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000214

Gnomad OTH

AF:

0.00984

GnomAD3 exomes

AF:

0.00249

AC:

520

AN:

208886

Hom.:

AF XY:

0.00190

AC XY:

217

AN XY:

114430

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000428

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000207

Gnomad OTH exome

AF:

0.00189

GnomAD4 exome

AF:

0.00102

AC:

1381

AN:

1349226

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

610

AN XY:

673126

show subpopulations

Gnomad4 AFR exome

AF:

0.0350

Gnomad4 AMR exome

AF:

0.00296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000122

Gnomad4 FIN exome

AF:

0.0000194

Gnomad4 NFE exome

AF:

0.0000929

Gnomad4 OTH exome

AF:

0.00290

GnomAD4 genome

AF:

0.00949

AC:

1339

AN:

141088

Hom.:

Cov.:

AF XY:

0.00928

AC XY:

631

AN XY:

67970

show subpopulations

Gnomad4 AFR

AF:

0.0319

Gnomad4 AMR

AF:

0.00579

Gnomad4 ASJ

AF:

0.000297

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000710

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000214

Gnomad4 OTH

AF:

0.00973

Alfa

AF:

0.000708

Hom.:

Asia WGS

AF:

0.00173

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.53

DANN

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00018

dbscSNV1_RF

Benign

0.14

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over