dbSNP rs753306232: RLIM:c.-23-12_-23-11delTT (chrX-74596010-GAA-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_016120.4(RLIM):c.-23-12_-23-11delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,040,001 control chromosomes in the GnomAD database, including 1 homozygotes. There are 387 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00089 ( 0 hom., 41 hem., cov: 23)

Exomes 𝑓: 0.0011 ( 1 hom. 346 hem. )

Consequence

RLIM
NM_016120.4 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.85

Publications

0 publications found

Variant links:

Genes affected

RLIM (HGNC:13429): (ring finger protein, LIM domain interacting) The protein encoded by this gene is a RING-H2 zinc finger protein. It has been shown to be an E3 ubiquitin protein ligase that targets LIM domain binding 1 (LDB1/CLIM), and causes proteasome-dependent degradation of LDB1. This protein and LDB1 are co-repressors of LHX1/LIM-1, a homeodomain transcription factor. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2009]

RLIM Gene-Disease associations (from GenCC):

non-syndromic X-linked intellectual disability
Inheritance: XL Classification: DEFINITIVE Submitted by: Illumina
intellectual disability, X-linked 61
Inheritance: XL Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Broad Center for Mendelian Genomics, G2P, Ambry Genetics
syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

RLIM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant X-74596010-GAA-G is Benign according to our data. Variant chrX-74596010-GAA-G is described in ClinVar as Likely_benign. ClinVar VariationId is 446076.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 100 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLIM	NM_016120.4 link	c.-23-12_-23-11delTT		intron_variant	Intron 1 of 3	ENST00000332687.11	NP_057204.2	Q9NVW2-1
RLIM	NM_183353.3 link	c.-23-12_-23-11delTT		intron_variant	Intron 2 of 4		NP_899196.1	Q9NVW2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLIM	ENST00000332687.11 link	c.-23-12_-23-11delTT		intron_variant	Intron 1 of 3	1	NM_016120.4	ENSP00000328059.6		Q9NVW2-1
RLIM	ENST00000349225.2 link	c.-23-12_-23-11delTT		intron_variant	Intron 2 of 4	2		ENSP00000253571.3		Q9NVW2-1

Frequencies

GnomAD3 genomes

AF:

0.000881

AC:

AN:

112413

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000969

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000564

Gnomad ASJ

AF:

0.00113

Gnomad EAS

AF:

0.00278

Gnomad SAS

AF:

0.00292

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000770

Gnomad OTH

AF:

0.00133

GnomAD2 exomes

AF:

0.00147

AC:

195

AN:

132280

AF XY:

0.00219

show subpopulations

Gnomad AFR exome

AF:

0.0000909

Gnomad AMR exome

AF:

0.000262

Gnomad ASJ exome

AF:

0.000880

Gnomad EAS exome

AF:

0.00263

Gnomad FIN exome

AF:

0.00348

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00110

AC:

1020

AN:

927538

Hom.:

AF XY:

0.00144

AC XY:

346

AN XY:

240350

show subpopulations

African (AFR)

AF:

0.000138

AC:

AN:

21797

American (AMR)

AF:

0.000338

AC:

AN:

23687

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

15948

East Asian (EAS)

AF:

0.000708

AC:

AN:

28245

South Asian (SAS)

AF:

0.00391

AC:

144

AN:

36869

European-Finnish (FIN)

AF:

0.00272

AC:

104

AN:

38227

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3567

European-Non Finnish (NFE)

AF:

0.000914

AC:

658

AN:

719558

Other (OTH)

AF:

0.00149

AC:

AN:

39640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

115

153

191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.000889

AC:

100

AN:

112463

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

34699

show subpopulations

African (AFR)

AF:

0.0000967

AC:

AN:

31021

American (AMR)

AF:

0.000564

AC:

AN:

10643

Ashkenazi Jewish (ASJ)

AF:

0.00113

AC:

AN:

2651

East Asian (EAS)

AF:

0.00278

AC:

AN:

3592

South Asian (SAS)

AF:

0.00330

AC:

AN:

2731

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

6130

Middle Eastern (MID)

AF:

0.00

AC:

AN:

218

European-Non Finnish (NFE)

AF:

0.000770

AC:

AN:

53269

Other (OTH)

AF:

0.00132

AC:

AN:

1519

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000498

Hom.:

Bravo

AF:

0.000567

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over