rs12137934

Positions:

• chr1-46263241-A-G

Variant summary

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

The ENST00000371975.9(RAD54L):​c.891+1856A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,090 control chromosomes in the GnomAD database, including 4,288 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 0.22 (4288 hom., cov: 32)
• Consequence: RAD54L ENST00000371975.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.225

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD54L	NM_003579.4	c.891+1856A>G		intron_variant		ENST00000371975.9	NP_003570.2
RAD54L	NM_001142548.2	c.891+1856A>G		intron_variant			NP_001136020.1
RAD54L	NM_001370766.1	c.351+1856A>G		intron_variant			NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9	c.891+1856A>G		intron_variant		1	NM_003579.4	ENSP00000361043	P1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33896 AN: 151972 Hom.: 4290 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.236

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.00904

Gnomad SAS AF: 0.0846

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.252

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.223 AC: 33900 AN: 152090 Hom.: 4288 Cov.: 32 AF XY: 0.218 AC XY: 16233 AN XY: 74328

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.00925

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.313

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.215

Alfa AF: 0.260 Hom.: 1639

Bravo AF: 0.214

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	9.2
DANN	Benign	0.60

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: rs12137934; hg19: chr1-46728913;