rs3019146

Positions:

• chr8-94401878-C-T

Variant summary

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

The ENST00000336148.10(RAD54B):​c.945-1415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 151,872 control chromosomes in the GnomAD database, including 12,251 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 0.40 (12251 hom., cov: 32)
• Consequence: RAD54B ENST00000336148.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50

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]

FSBP (HGNC:43653): (fibrinogen silencer binding protein) Enables identical protein binding activity. Located in nucleoplasm. [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=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD54B	NM_012415.3	c.945-1415G>A		intron_variant		ENST00000336148.10	NP_036547.1
RAD54B	NM_001205263.2	c.393-1415G>A		intron_variant			NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54B	ENST00000336148.10	c.945-1415G>A		intron_variant		1	NM_012415.3	ENSP00000336606	P1
RAD54B	ENST00000463267.5	c.*625-1415G>A		intron_variant, NMD_transcript_variant		1		ENSP00000430808
FSBP	ENST00000517506.2	c.*625-1415G>A		intron_variant, NMD_transcript_variant		5		ENSP00000462684

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60607 AN: 151754 Hom.: 12246 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.399 AC: 60643 AN: 151872 Hom.: 12251 Cov.: 32 AF XY: 0.406 AC XY: 30127 AN XY: 74224

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.470

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.369

Gnomad4 OTH AF: 0.425

Alfa AF: 0.384 Hom.: 5449

Bravo AF: 0.407

Asia WGS AF: 0.421 AC: 1465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.37

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: rs3019146; hg19: chr8-95414106;