NM_003579.4:c.1869+822A>G

Variant names:

• chr1-46275539-A-G
• rs17102098
• NM_003579.4:c.1869+822A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003579.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54L	NM_003579.4	MANE Select	c.1869+822A>G		intron	N/A	NP_003570.2
	RAD54L	NM_001142548.2		c.1869+822A>G		intron	N/A	NP_001136020.1
	RAD54L	NM_001370766.1		c.1329+822A>G		intron	N/A	NP_001357695.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54L	ENST00000371975.9	TSL:1 MANE Select	c.1869+822A>G		intron	N/A	ENSP00000361043.4
	RAD54L	ENST00000932547.1		c.1899+822A>G		intron	N/A	ENSP00000602606.1
	RAD54L	ENST00000442598.5	TSL:2	c.1869+822A>G		intron	N/A	ENSP00000396113.1

Frequencies

GnomAD3 genomes AF: 0.0598 AC: 9079 AN: 151832 Hom.: 551 Cov.: 32

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.: 32 AF XY: 0.0610 AC XY: 4528 AN XY: 74286

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: 80 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: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1286 AN: 67940

Other (OTH) AF: 0.0455 AC: 96 AN: 2110

Alfa AF: 0.0479 Hom.: 45

Bravo AF: 0.0603

Asia WGS AF: 0.0510 AC: 178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.72
PhyloP100		-0.95
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: rs17102098; hg19: chr1-46741211;