NM_003579.4:c.2190C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003579.4(RAD54L):c.2190C>T(p.Ala730Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,613,356 control chromosomes in the GnomAD database, including 17,922 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1240 hom., cov: 32)

Exomes 𝑓: 0.13 ( 16682 hom. )

Consequence

RAD54L
NM_003579.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.21

Publications

35 publications found

Variant links:

Genes affected

RAD54L (HGNC:9826): (RAD54 like) The protein encoded by this gene belongs to the DEAD-like helicase superfamily, and shares similarity with Saccharomyces cerevisiae Rad54, a protein known to be involved in the homologous recombination and repair of DNA. This protein has been shown to play a role in homologous recombination related repair of DNA double-strand breaks. The binding of this protein to double-strand DNA induces a DNA topological change, which is thought to facilitate homologous DNA paring, and stimulate DNA recombination. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]

RAD54L links:

LRRC41 (HGNC:16917): (leucine rich repeat containing 41) Predicted to enable identical protein binding activity. Predicted to be involved in protein ubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-46278228-C-T is Benign according to our data. Variant chr1-46278228-C-T is described in ClinVar as Benign. ClinVar VariationId is 1678943.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
RAD54L	NM_003579.4 link	c.2190C>T	p.Ala730Ala	synonymous_variant	Exon 18 of 18	ENST00000371975.9	NP_003570.2
LRRC41	NM_006369.5 link	c.*637G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000617190.5	NP_006360.3
RAD54L	NM_001142548.2 link	c.2190C>T	p.Ala730Ala	synonymous_variant	Exon 19 of 19		NP_001136020.1
RAD54L	NM_001370766.1 link	c.1650C>T	p.Ala550Ala	synonymous_variant	Exon 18 of 18		NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9 link	c.2190C>T	p.Ala730Ala	synonymous_variant	Exon 18 of 18	1	NM_003579.4	ENSP00000361043.4
LRRC41	ENST00000617190.5 link	c.*637G>A		3_prime_UTR_variant	Exon 10 of 10	1	NM_006369.5	ENSP00000477792.1

Frequencies

GnomAD3 genomes

AF:

0.108

AC:

16389

AN:

151962

Hom.:

1239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0438

Gnomad AMI

AF:

0.100

Gnomad AMR

AF:

0.0995

Gnomad ASJ

AF:

0.131

Gnomad EAS

AF:

0.306

Gnomad SAS

AF:

0.372

Gnomad FIN

AF:

0.0848

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.116

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.152

AC:

37888

AN:

250040

AF XY:

0.166

show subpopulations

Gnomad AFR exome

AF:

0.0419

Gnomad AMR exome

AF:

0.0962

Gnomad ASJ exome

AF:

0.125

Gnomad EAS exome

AF:

0.299

Gnomad FIN exome

AF:

0.0902

Gnomad NFE exome

AF:

0.116

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.132

AC:

193512

AN:

1461276

Hom.:

16682

Cov.:

AF XY:

0.140

AC XY:

101963

AN XY:

726888

show subpopulations

African (AFR)

AF:

0.0427

AC:

1428

AN:

33476

American (AMR)

AF:

0.0950

AC:

4242

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.125

AC:

3277

AN:

26124

East Asian (EAS)

AF:

0.324

AC:

12850

AN:

39672

South Asian (SAS)

AF:

0.365

AC:

31407

AN:

86120

European-Finnish (FIN)

AF:

0.0938

AC:

5007

AN:

53370

Middle Eastern (MID)

AF:

0.218

AC:

1254

AN:

5754

European-Non Finnish (NFE)

AF:

0.113

AC:

125804

AN:

1111724

Other (OTH)

AF:

0.137

AC:

8243

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

10902

21804

32705

43607

54509

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4780

9560

14340

19120

23900

<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:

0.108

AC:

16390

AN:

152080

Hom.:

1240

Cov.:

AF XY:

0.113

AC XY:

8387

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0436

AC:

1811

AN:

41528

American (AMR)

AF:

0.0994

AC:

1520

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.131

AC:

453

AN:

3470

East Asian (EAS)

AF:

0.307

AC:

1579

AN:

5148

South Asian (SAS)

AF:

0.372

AC:

1794

AN:

4828

European-Finnish (FIN)

AF:

0.0848

AC:

899

AN:

10598

Middle Eastern (MID)

AF:

0.177

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.116

AC:

7892

AN:

67910

Other (OTH)

AF:

0.142

AC:

299

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

725

1450

2174

2899

3624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

208

416

624

832

1040

<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:

0.118

Hom.:

3462

Bravo

AF:

0.101

Asia WGS

AF:

0.298

AC:

1034

AN:

3478

EpiCase

AF:

0.125

EpiControl

AF:

0.125

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 22, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

RAD54L-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

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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