Genetic Variant RSL1D1:c.384+7A>T (chr16-11847661-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Publications

1 publications found

Variant links:

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]

RSL1D1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2646231.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015659.3. 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
	RSL1D1	NM_015659.3	MANE Select	c.384+7A>T		splice_region intron	N/A	NP_056474.2	O76021-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RSL1D1	ENST00000571133.6	TSL:1 MANE Select	c.384+7A>T	splice_region intron	N/A	ENSP00000460871.1	O76021-1
RSL1D1	ENST00000355674.9	TSL:1	c.384+7A>T	splice_region intron	N/A	ENSP00000347897.5	J3QSV6
RSL1D1	ENST00000898748.1		c.384+7A>T	splice_region intron	N/A	ENSP00000568807.1

Frequencies

GnomAD3 genomes

AF:

0.00280

AC:

427

AN:

152244

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00383

AC:

941

AN:

245550

AF XY:

0.00442

show subpopulations

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 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.:

Cov.:

AF XY:

0.00461

AC XY:

3327

AN XY:

721932

show subpopulations

African (AFR)

AF:

0.00137

AC:

AN:

32964

American (AMR)

AF:

0.00173

AC:

AN:

42274

Ashkenazi Jewish (ASJ)

AF:

0.00274

AC:

AN:

25916

East Asian (EAS)

AF:

0.0000506

AC:

AN:

39564

South Asian (SAS)

AF:

0.00964

AC:

817

AN:

84728

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

53246

Middle Eastern (MID)

AF:

0.00889

AC:

AN:

5176

European-Non Finnish (NFE)

AF:

0.00446

AC:

4937

AN:

1107822

Other (OTH)

AF:

0.00438

AC:

263

AN:

60004

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

273

547

820

1094

1367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

190

380

570

760

950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00281

AC:

428

AN:

152362

Hom.:

Cov.:

AF XY:

0.00287

AC XY:

214

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.000962

AC:

AN:

41586

American (AMR)

AF:

0.00196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00972

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00404

AC:

275

AN:

68042

Other (OTH)

AF:

0.00520

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00384

Hom.:

Bravo

AF:

0.00277

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00445

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

1.3

(source)

DANN

Benign

0.79

PhyloP100

-0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over