dbSNP rs61239976: RAD54L:c.767-57G>T (chr1-46261204-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003579.4(RAD54L):c.767-57G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,340,506 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 27 hom., cov: 31)

Exomes 𝑓: 0.0016 ( 18 hom. )

Consequence

RAD54L
NM_003579.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.916

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-46261204-G-T is Benign according to our data. Variant chr1-46261204-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1679090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00942 (1305/138476) while in subpopulation AFR AF= 0.0306 (1131/36910). AF 95% confidence interval is 0.0292. There are 27 homozygotes in gnomad4. There are 633 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RAD54L	NM_003579.4 link	c.767-57G>T	intron_variant	Intron 7 of 17	ENST00000371975.9	NP_003570.2	Q92698
RAD54L	NM_001142548.2 link	c.767-57G>T	intron_variant	Intron 8 of 18		NP_001136020.1	Q92698A8K996
RAD54L	NM_001370766.1 link	c.227-57G>T	intron_variant	Intron 7 of 17		NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9 link	c.767-57G>T		intron_variant	Intron 7 of 17	1	NM_003579.4	ENSP00000361043.4		Q92698

Frequencies

GnomAD3 genomes

AF:

0.00940

AC:

1302

AN:

138460

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0306

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00310

Gnomad ASJ

AF:

0.00943

Gnomad EAS

AF:

0.000841

Gnomad SAS

AF:

0.0119

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0203

Gnomad NFE

AF:

0.000438

Gnomad OTH

AF:

0.00579

GnomAD4 exome

AF:

0.00163

AC:

1965

AN:

1202030

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

1143

AN XY:

603614

show subpopulations

Gnomad4 AFR exome

AF:

0.0246

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.00653

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.00908

Gnomad4 FIN exome

AF:

0.000325

Gnomad4 NFE exome

AF:

0.000212

Gnomad4 OTH exome

AF:

0.00269

GnomAD4 genome

AF:

0.00942

AC:

1305

AN:

138476

Hom.:

Cov.:

AF XY:

0.00943

AC XY:

633

AN XY:

67110

show subpopulations

Gnomad4 AFR

AF:

0.0306

Gnomad4 AMR

AF:

0.00310

Gnomad4 ASJ

AF:

0.00943

Gnomad4 EAS

AF:

0.000843

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000438

Gnomad4 OTH

AF:

0.00576

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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: Likely 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

-0.94

CADD

Benign

0.54

DANN

Benign

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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