8-94450467-C-T

Variant names:

• chr8-94450467-C-T
• rs2930968
• NM_012415.3:c.304+7801G>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.304+7801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 152,056 control chromosomes in the GnomAD database, including 13,322 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 0.42 (13322 hom., cov: 32)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD54B	NM_012415.3	c.304+7801G>A		intron_variant	Intron 3 of 14	ENST00000336148.10	NP_036547.1
RAD54B	NM_001205262.3	c.304+7801G>A		intron_variant	Intron 3 of 3		NP_001192191.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD54B	ENST00000336148.10	c.304+7801G>A		intron_variant	Intron 3 of 14	1	NM_012415.3	ENSP00000336606.5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63061 AN: 151938 Hom.: 13312 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.415 AC: 63109 AN: 152056 Hom.: 13322 Cov.: 32 AF XY: 0.422 AC XY: 31349 AN XY: 74320

African (AFR) AF: 0.434 AC: 18015 AN: 41472

American (AMR) AF: 0.512 AC: 7816 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2414 AN: 5164

South Asian (SAS) AF: 0.425 AC: 2052 AN: 4824

European-Finnish (FIN) AF: 0.444 AC: 4687 AN: 10550

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.375 AC: 25501 AN: 67998

Other (OTH) AF: 0.431 AC: 912 AN: 2114

Alfa AF: 0.408 Hom.: 1648

Bravo AF: 0.423

Asia WGS AF: 0.428 AC: 1490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.60
PhyloP100		-0.040
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: rs2930968; hg19: chr8-95462695;