chr8-94401878-C-T

Variant names:

• chr8-94401878-C-T
• rs3019146
• NM_012415.3:c.945-1415G>A

Variant summary

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

The NM_012415.3(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 NM_012415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.50
• Publications: 3 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]

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

Our verdict: Benign. The variant received -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.

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.945-1415G>A		intron	N/A	NP_036547.1
	RAD54B	NM_001205263.2		c.393-1415G>A		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.945-1415G>A		intron	N/A	ENSP00000336606.5
	RAD54B	ENST00000463267.5	TSL:1	n.*625-1415G>A		intron	N/A	ENSP00000430808.1
	FSBP	ENST00000517506.2	TSL:5	n.*625-1415G>A		intron	N/A	ENSP00000462684.1

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

African (AFR) AF: 0.399 AC: 16491 AN: 41360

American (AMR) AF: 0.504 AC: 7688 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1290 AN: 3466

East Asian (EAS) AF: 0.470 AC: 2429 AN: 5172

South Asian (SAS) AF: 0.424 AC: 2041 AN: 4812

European-Finnish (FIN) AF: 0.410 AC: 4322 AN: 10540

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25070 AN: 67954

Other (OTH) AF: 0.425 AC: 895 AN: 2108

Alfa AF: 0.383 Hom.: 6022

Bravo AF: 0.407

Asia WGS AF: 0.421 AC: 1465 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.37
PhyloP100		-3.5
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: rs3019146; hg19: chr8-95414106;