NM_015056.3:c.358-8T>A

Variant names:

• chr21-43674628-T-A
• rs114577524
• NM_015056.3:c.358-8T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Publications: 2 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: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 25 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1B	NM_015056.3	MANE Select	c.358-8T>A		splice_region intron	N/A	NP_055871.1	Q14684-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1B	ENST00000340648.6	TSL:1 MANE Select	c.358-8T>A		splice_region intron	N/A	ENSP00000339145.4	Q14684-1

Frequencies

GnomAD3 genomes AF: 0.00946 AC: 1333 AN: 140982 Hom.: 23 Cov.: 25

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

GnomAD2 exomes AF: 0.00249 AC: 520 AN: 208886 AF XY: 0.00190

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 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.: 22 Cov.: 28 AF XY: 0.000906 AC XY: 610 AN XY: 673126

African (AFR) AF: 0.0350 AC: 1008 AN: 28790

American (AMR) AF: 0.00296 AC: 88 AN: 29724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23238

East Asian (EAS) AF: 0.00 AC: 0 AN: 37194

South Asian (SAS) AF: 0.000122 AC: 9 AN: 74028

European-Finnish (FIN) AF: 0.0000194 AC: 1 AN: 51542

Middle Eastern (MID) AF: 0.00314 AC: 17 AN: 5410

European-Non Finnish (NFE) AF: 0.0000929 AC: 97 AN: 1043700

Other (OTH) AF: 0.00290 AC: 161 AN: 55600

GnomAD4 genome AF: 0.00949 AC: 1339 AN: 141088 Hom.: 25 Cov.: 25 AF XY: 0.00928 AC XY: 631 AN XY: 67970

African (AFR) AF: 0.0319 AC: 1225 AN: 38452

American (AMR) AF: 0.00579 AC: 77 AN: 13310

Ashkenazi Jewish (ASJ) AF: 0.000297 AC: 1 AN: 3362

East Asian (EAS) AF: 0.00 AC: 0 AN: 4494

South Asian (SAS) AF: 0.000710 AC: 3 AN: 4228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8686

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 276

European-Non Finnish (NFE) AF: 0.000214 AC: 14 AN: 65462

Other (OTH) AF: 0.00973 AC: 19 AN: 1952

Alfa AF: 0.000708 Hom.: 1

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.53
DANN	Benign	0.36
PhyloP100		-0.94
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114577524; hg19: chr21-45094509;