rs2046666

Variant names:

• chr8-94375920-G-A
• rs2046666
• NM_012415.3:c.2515+2260C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-94375920-G-A
• chr8-94375920-G-T

Variant summary

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

The NM_012415.3(RAD54B):​c.2515+2260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,140 control chromosomes in the GnomAD database, including 17,382 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 0.46 (17382 hom., cov: 31)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0640
• Publications: 4 publications found

Genes affected

RAD54B (HGNC:17228): (RAD54 homolog B) The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with Saccharomyces cerevisiae RAD54 and RDH54, both of which are involved in homologous recombination and repair of DNA. This protein binds to double-stranded DNA, and displays ATPase activity in the presence of DNA. This gene is highly expressed in testis and spleen, which suggests active roles in meiotic and mitotic recombination. Homozygous mutations of this gene were observed in primary lymphoma and colon cancer. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012415.3. 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
	RAD54B	NM_012415.3	MANE Select	c.2515+2260C>T		intron	N/A	NP_036547.1
	RAD54B	NM_001205263.2		c.1963+2260C>T		intron	N/A	NP_001192192.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54B	ENST00000336148.10	TSL:1 MANE Select	c.2515+2260C>T		intron	N/A	ENSP00000336606.5

Frequencies

GnomAD3 genomes AF: 0.456 AC: 68941 AN: 151028 Hom.: 17380 Cov.: 31

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.456 AC: 68974 AN: 151140 Hom.: 17382 Cov.: 31 AF XY: 0.451 AC XY: 33323 AN XY: 73896

African (AFR) AF: 0.256 AC: 10436 AN: 40750

American (AMR) AF: 0.405 AC: 6168 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1920 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1087 AN: 5168

South Asian (SAS) AF: 0.420 AC: 2023 AN: 4812

European-Finnish (FIN) AF: 0.562 AC: 5916 AN: 10524

Middle Eastern (MID) AF: 0.455 AC: 133 AN: 292

European-Non Finnish (NFE) AF: 0.586 AC: 39805 AN: 67890

Other (OTH) AF: 0.459 AC: 961 AN: 2094

Alfa AF: 0.505 Hom.: 2840

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.21
PhyloP100		0.064
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: rs2046666; hg19: chr8-95388148;