dbSNP rs17102098: RAD54L:c.1869+822A>G (chr1-46275539-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003579.4(RAD54L):c.1869+822A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 151,950 control chromosomes in the GnomAD database, including 552 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.060 ( 552 hom., cov: 32)

Consequence

RAD54L
NM_003579.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.949

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RAD54L	NM_003579.4 link	c.1869+822A>G	intron_variant	Intron 16 of 17	ENST00000371975.9	NP_003570.2	Q92698
RAD54L	NM_001142548.2 link	c.1869+822A>G	intron_variant	Intron 17 of 18		NP_001136020.1	Q92698A8K996
RAD54L	NM_001370766.1 link	c.1329+822A>G	intron_variant	Intron 16 of 17		NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9 link	c.1869+822A>G		intron_variant	Intron 16 of 17	1	NM_003579.4	ENSP00000361043.4		Q92698

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

9079

AN:

151832

Hom.:

551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.0154

Gnomad SAS

AF:

0.0623

Gnomad FIN

AF:

0.0667

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0189

Gnomad OTH

AF:

0.0460

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0598

AC:

9091

AN:

151950

Hom.:

552

Cov.:

AF XY:

0.0610

AC XY:

4528

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.146

AC:

6040

AN:

41432

American (AMR)

AF:

0.0283

AC:

432

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0375

AC:

130

AN:

3466

East Asian (EAS)

AF:

0.0155

AC:

AN:

5176

South Asian (SAS)

AF:

0.0626

AC:

300

AN:

4796

European-Finnish (FIN)

AF:

0.0667

AC:

704

AN:

10554

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0189

AC:

1286

AN:

67940

Other (OTH)

AF:

0.0455

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

416

832

1249

1665

2081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0479

Hom.:

Bravo

AF:

0.0603

Asia WGS

AF:

0.0510

AC:

178

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.77

(source)

DANN

Benign

0.72

PhyloP100

-0.95

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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rs17102098

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over