Genetic Variant RAD54B:c.2247+318G>A (chr8-94379827-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_012415.3(RAD54B):c.2247+318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,006 control chromosomes in the GnomAD database, including 12,475 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.40 ( 12475 hom., cov: 32)

Consequence

RAD54B
NM_012415.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.596

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 8-94379827-C-T is Benign according to our data. Variant chr8-94379827-C-T is described in ClinVar as Benign. ClinVar VariationId is 1229467.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54B	NM_012415.3	MANE Select	c.2247+318G>A		intron	N/A	NP_036547.1	Q9Y620-1
	RAD54B	NM_001205263.2		c.1695+318G>A		intron	N/A	NP_001192192.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD54B	ENST00000336148.10	TSL:1 MANE Select	c.2247+318G>A	intron	N/A	ENSP00000336606.5	Q9Y620-1
RAD54B	ENST00000911517.1		c.2247+318G>A	intron	N/A	ENSP00000581576.1
RAD54B	ENST00000911516.1		c.2247+318G>A	intron	N/A	ENSP00000581575.1

Frequencies

GnomAD3 genomes

AF:

0.403

AC:

61172

AN:

151888

Hom.:

12466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.404

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.468

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.410

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.371

Gnomad OTH

AF:

0.433

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

GnomAD4 genome

AF:

0.403

AC:

61217

AN:

152006

Hom.:

12475

Cov.:

AF XY:

0.409

AC XY:

30403

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.404

AC:

16740

AN:

41460

American (AMR)

AF:

0.510

AC:

7788

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1363

AN:

3472

East Asian (EAS)

AF:

0.467

AC:

2414

AN:

5164

South Asian (SAS)

AF:

0.423

AC:

2041

AN:

4820

European-Finnish (FIN)

AF:

0.410

AC:

4322

AN:

10548

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.371

AC:

25227

AN:

67952

Other (OTH)

AF:

0.430

AC:

907

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1902

3804

5706

7608

9510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.364

Hom.:

3860

Bravo

AF:

0.412

Asia WGS

AF:

0.423

AC:

1470

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

(source)

DANN

Benign

0.27

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over