chr21-43797542-C-T

Variant names:

• chr21-43797542-C-T
• rs142644786
• NM_003683.6:c.543C>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3 BP6_Very_Strong BS1 BS2

The NM_003683.6(RRP1):​c.543C>T​(p.Gly181Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000989 in 1,613,850 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00094 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (13 hom.)
• Consequence: RRP1 NM_003683.6 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.259
• Publications: 2 publications found

Genes affected

RRP1 (HGNC:18785): (ribosomal RNA processing 1) The protein encoded by this gene is the putative homolog of the yeast ribosomal RNA processing protein RRP1. The encoded protein is involved in the late stages of nucleologenesis at the end of mitosis, and may be required for the generation of 28S rRNA. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant 21-43797542-C-T is Benign according to our data. Variant chr21-43797542-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 731015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.000994 (1453/1461606) while in subpopulation MID AF = 0.0316 (182/5768). AF 95% confidence interval is 0.0278. There are 13 homozygotes in GnomAdExome4. There are 822 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003683.6. 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
	RRP1	NM_003683.6	MANE Select	c.543C>T	p.Gly181Gly	synonymous	Exon 6 of 13	NP_003674.1	P56182

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RRP1	ENST00000497547.2	TSL:1 MANE Select	c.543C>T	p.Gly181Gly	synonymous	Exon 6 of 13	ENSP00000417464.1	P56182
	RRP1	ENST00000467112.5	TSL:1	n.657C>T		non_coding_transcript_exon	Exon 3 of 10
	RRP1	ENST00000471909.1	TSL:1	n.182C>T		non_coding_transcript_exon	Exon 1 of 8

Frequencies

GnomAD3 genomes AF: 0.000940 AC: 143 AN: 152126 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00106 AC: 263 AN: 248954 AF XY: 0.00121

Gnomad AFR exome AF: 0.000323

Gnomad AMR exome AF: 0.000928

Gnomad ASJ exome AF: 0.000995

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000931

Gnomad NFE exome AF: 0.00120

Gnomad OTH exome AF: 0.00348

GnomAD4 exome AF: 0.000994 AC: 1453 AN: 1461606 Hom.: 13 Cov.: 31 AF XY: 0.00113 AC XY: 822 AN XY: 727094

African (AFR) AF: 0.00182 AC: 61 AN: 33480

American (AMR) AF: 0.00127 AC: 57 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 30 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00237 AC: 204 AN: 86248

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53364

Middle Eastern (MID) AF: 0.0316 AC: 182 AN: 5768

European-Non Finnish (NFE) AF: 0.000670 AC: 745 AN: 1111828

Other (OTH) AF: 0.00283 AC: 171 AN: 60370

GnomAD4 genome AF: 0.000939 AC: 143 AN: 152244 Hom.: 1 Cov.: 32 AF XY: 0.00105 AC XY: 78 AN XY: 74452

African (AFR) AF: 0.000289 AC: 12 AN: 41526

American (AMR) AF: 0.00262 AC: 40 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00231 AC: 8 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00332 AC: 16 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2114

Alfa AF: 0.000976 Hom.: 0

Bravo AF: 0.000997

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.00229

EpiControl AF: 0.00231

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Benign	0.80
PhyloP100		0.26
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.75		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.75		Position offset: -6

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

Other links and lift over

dbSNP: rs142644786; hg19: chr21-45217423;