8-94375920-G-A

Position:

• chr8-94375920-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD54B	NM_012415.3	c.2515+2260C>T		intron_variant		ENST00000336148.10	NP_036547.1
RAD54B	NM_001205263.2	c.1963+2260C>T		intron_variant			NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54B	ENST00000336148.10	c.2515+2260C>T		intron_variant		1	NM_012415.3	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

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.459

Alfa AF: 0.514 Hom.: 2796

Bravo AF: 0.432

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.21

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: rs2046666; hg19: chr8-95388148;