rs12410307

chr1-46264726-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003579.4(RAD54L):c.892-2733G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,326 control chromosomes in the GnomAD database, including 492 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 0.067 (492 hom., cov: 32)
• Consequence: RAD54L NM_003579.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.410

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0979 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54L	NM_003579.4	c.892-2733G>A		intron_variant		ENST00000371975.9
RAD54L	NM_001142548.2	c.892-2733G>A		intron_variant
RAD54L	NM_001370766.1	c.352-2733G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54L	ENST00000371975.9	c.892-2733G>A		intron_variant		1	NM_003579.4	P1

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10255 AN: 152208 Hom.: 494 Cov.: 32

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0711

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0674

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0999

Gnomad OTH AF: 0.0856

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

GnomAD4 genome AF: 0.0673 AC: 10245 AN: 152326 Hom.: 492 Cov.: 32 AF XY: 0.0650 AC XY: 4843 AN XY: 74490

Gnomad4 AFR AF: 0.0178

Gnomad4 AMR AF: 0.0709

Gnomad4 ASJ AF: 0.124

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0674

Gnomad4 NFE AF: 0.0999

Gnomad4 OTH AF: 0.0847

Alfa AF: 0.0869 Hom.: 377

Bravo AF: 0.0658

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.88

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

Other links and lift over

dbSNP: rs12410307; hg19: chr1-46730398;