rs12410307

Variant names:

• chr1-46264726-G-A
• rs12410307
• NM_003579.4:c.892-2733G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD54L	NM_003579.4	c.892-2733G>A		intron_variant	Intron 8 of 17	ENST00000371975.9	NP_003570.2
RAD54L	NM_001142548.2	c.892-2733G>A		intron_variant	Intron 9 of 18		NP_001136020.1
RAD54L	NM_001370766.1	c.352-2733G>A		intron_variant	Intron 8 of 17		NP_001357695.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54L	ENST00000371975.9	c.892-2733G>A		intron_variant	Intron 8 of 17	1	NM_003579.4	ENSP00000361043.4

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

African (AFR) AF: 0.0178 AC: 739 AN: 41584

American (AMR) AF: 0.0709 AC: 1085 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0207 AC: 100 AN: 4822

European-Finnish (FIN) AF: 0.0674 AC: 716 AN: 10618

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0999 AC: 6793 AN: 68024

Other (OTH) AF: 0.0847 AC: 179 AN: 2114

Alfa AF: 0.0850 Hom.: 515

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
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12410307; hg19: chr1-46730398;