8-94408822-C-A

Position:

• chr8-94408822-C-A

Variant summary

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

The NM_012415.3(RAD54B):​c.500-1102G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,120 control chromosomes in the GnomAD database, including 1,163 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 0.091 (1163 hom., cov: 32)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.754

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD54B	NM_012415.3	c.500-1102G>T		intron_variant		ENST00000336148.10	NP_036547.1
RAD54B	NM_001205263.2	c.-53-1102G>T		intron_variant			NP_001192192.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD54B	ENST00000336148.10	c.500-1102G>T		intron_variant		1	NM_012415.3	ENSP00000336606.5
RAD54B	ENST00000463267.5	n.*180-1102G>T		intron_variant		1		ENSP00000430808.1
FSBP	ENST00000517506.2	n.*180-1102G>T		intron_variant		5		ENSP00000462684.1
RAD54B	ENST00000518998.5	n.*172-1102G>T		intron_variant		3		ENSP00000430570.1

Frequencies

GnomAD3 genomes AF: 0.0913 AC: 13885 AN: 152002 Hom.: 1159 Cov.: 32

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0260

Gnomad OTH AF: 0.0893

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

GnomAD4 genome AF: 0.0914 AC: 13905 AN: 152120 Hom.: 1163 Cov.: 32 AF XY: 0.0930 AC XY: 6914 AN XY: 74346

Gnomad4 AFR AF: 0.207

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.0338

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.0254

Gnomad4 NFE AF: 0.0260

Gnomad4 OTH AF: 0.0884

Alfa AF: 0.0675 Hom.: 87

Bravo AF: 0.104

Asia WGS AF: 0.0780 AC: 270 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.2
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10504937; hg19: chr8-95421050;