1-46278228-C-T

Position:

chr1-46278228-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003579.4(RAD54L):c.2190C>T(p.Ala730=) 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein
RAD54L	NM_003579.4 linkuse as main transcript	c.2190C>T	p.Ala730=	synonymous_variant	18/18	ENST00000371975.9	NP_003570.2
LRRC41	NM_006369.5 linkuse as main transcript	c.*637G>A		3_prime_UTR_variant	10/10	ENST00000617190.5	NP_006360.3
RAD54L	NM_001142548.2 linkuse as main transcript	c.2190C>T	p.Ala730=	synonymous_variant	19/19		NP_001136020.1
RAD54L	NM_001370766.1 linkuse as main transcript	c.1650C>T	p.Ala550=	synonymous_variant	18/18		NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9 linkuse as main transcript	c.2190C>T	p.Ala730=	synonymous_variant	18/18	1	NM_003579.4	ENSP00000361043	P1
LRRC41	ENST00000617190.5 linkuse as main transcript	c.*637G>A		3_prime_UTR_variant	10/10	1	NM_006369.5	ENSP00000477792	P1	Q15345-2

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

GnomAD3 exomes

AF:

0.152

AC:

37888

AN:

250040

Hom.:

4144

AF XY:

0.166

AC XY:

22406

AN XY:

135206

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 SAS exome

AF:

0.369

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

Gnomad4 AFR exome

AF:

0.0427

Gnomad4 AMR exome

AF:

0.0950

Gnomad4 ASJ exome

AF:

0.125

Gnomad4 EAS exome

AF:

0.324

Gnomad4 SAS exome

AF:

0.365

Gnomad4 FIN exome

AF:

0.0938

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.137

GnomAD4 genome

AF:

0.108

AC:

16390

AN:

152080

Hom.:

1240

Cov.:

AF XY:

0.113

AC XY:

8387

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0436

Gnomad4 AMR

AF:

0.0994

Gnomad4 ASJ

AF:

0.131

Gnomad4 EAS

AF:

0.307

Gnomad4 SAS

AF:

0.372

Gnomad4 FIN

AF:

0.0848

Gnomad4 NFE

AF:

0.116

Gnomad4 OTH

AF:

0.142

Alfa

AF:

0.121

Hom.:

2420

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

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2019

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

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

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over