dbSNP rs10504937: RAD54B:c.500-1102G>T (chr8-94408822-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.754

Publications

1 publications found

Variant links:

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]

RAD54B links:

FSBP (HGNC:43653): (fibrinogen silencer binding protein) Enables identical protein binding activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FSBP links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD54B	NM_012415.3 link	c.500-1102G>T		intron_variant	Intron 4 of 14	ENST00000336148.10	NP_036547.1	Q9Y620-1
RAD54B	NM_001205263.2 link	c.-53-1102G>T		intron_variant	Intron 2 of 12		NP_001192192.1	Q9Y620

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAD54B	ENST00000336148.10 link	c.500-1102G>T	intron_variant	Intron 4 of 14	1	NM_012415.3	ENSP00000336606.5	Q9Y620-1
RAD54B	ENST00000463267.5 link	n.*180-1102G>T	intron_variant	Intron 5 of 10	1		ENSP00000430808.1	E5RI14
FSBP	ENST00000517506.2 link	n.*180-1102G>T	intron_variant	Intron 2 of 11	5		ENSP00000462684.1	J3KSW4
RAD54B	ENST00000518998.5 link	n.*172-1102G>T	intron_variant	Intron 3 of 3	3		ENSP00000430570.1	E5RJF7

Frequencies

GnomAD3 genomes

AF:

0.0913

AC:

13885

AN:

152002

Hom.:

1159

Cov.:

show subpopulations

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.:

AF XY:

0.0930

AC XY:

6914

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.207

AC:

8585

AN:

41462

American (AMR)

AF:

0.148

AC:

2262

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.0452

AC:

157

AN:

3472

East Asian (EAS)

AF:

0.0338

AC:

175

AN:

5178

South Asian (SAS)

AF:

0.0906

AC:

437

AN:

4822

European-Finnish (FIN)

AF:

0.0254

AC:

269

AN:

10604

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0260

AC:

1767

AN:

67982

Other (OTH)

AF:

0.0884

AC:

187

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

583

1165

1748

2330

2913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0738

Hom.:

111

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

(source)

DANN

Benign

0.74

PhyloP100

-0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over