16-11847661-T-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_015659.3(RSL1D1):c.384+7A>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00421 in 1,604,056 control chromosomes in the GnomAD database, including 26 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0044 (26 hom.)
• Consequence: RSL1D1 NM_015659.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001635
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

Genes affected

RSL1D1 (HGNC:24534): (ribosomal L1 domain containing 1) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Involved in regulation of apoptotic process and regulation of cellular senescence. Acts upstream of or within regulation of protein localization. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 16-11847661-T-A is Benign according to our data. Variant chr16-11847661-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2646231.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSL1D1	NM_015659.3	c.384+7A>T		splice_region_variant, intron_variant		ENST00000571133.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSL1D1	ENST00000571133.6	c.384+7A>T		splice_region_variant, intron_variant		1	NM_015659.3	P1

Frequencies

GnomAD3 genomes AF: 0.00280 AC: 427 AN: 152244 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00951

Gnomad FIN AF: 0.000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00404

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00383 AC: 941 AN: 245550 Hom.: 4 AF XY: 0.00442 AC XY: 587 AN XY: 132892

Gnomad AFR exome AF: 0.000868

Gnomad AMR exome AF: 0.00148

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00908

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00472

Gnomad OTH exome AF: 0.00548

GnomAD4 exome AF: 0.00436 AC: 6330 AN: 1451694 Hom.: 26 Cov.: 29 AF XY: 0.00461 AC XY: 3327 AN XY: 721932

Gnomad4 AFR exome AF: 0.00137

Gnomad4 AMR exome AF: 0.00173

Gnomad4 ASJ exome AF: 0.00274

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.00964

Gnomad4 FIN exome AF: 0.00143

Gnomad4 NFE exome AF: 0.00446

Gnomad4 OTH exome AF: 0.00438

GnomAD4 genome AF: 0.00281 AC: 428 AN: 152362 Hom.: 0 Cov.: 33 AF XY: 0.00287 AC XY: 214 AN XY: 74506

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00403

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00972

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00404

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.00384 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00496

EpiControl AF: 0.00445

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

RSL1D1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.3
Dann	Benign	0.79
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00016
dbscSNV1_RF	Benign	0.0020
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

Other links and lift over

dbSNP: rs71383294; hg19: chr16-11941518;