8-94392147-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012415.3(RAD54B):c.1519-248T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,210 control chromosomes in the GnomAD database, including 2,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.14 (2062 hom., cov: 31)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-94392147-A-C is Benign according to our data. Variant chr8-94392147-A-C is described in ClinVar as [Benign]. Clinvar id is 1228218.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54B	NM_012415.3	c.1519-248T>G		intron_variant		ENST00000336148.10
RAD54B	NM_001205263.2	c.967-248T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54B	ENST00000336148.10	c.1519-248T>G		intron_variant		1	NM_012415.3	P1
RAD54B	ENST00000463267.5	c.*1143-248T>G		intron_variant, NMD_transcript_variant		1
FSBP	ENST00000517506.2	c.*1199-248T>G		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20750 AN: 152092 Hom.: 2059 Cov.: 31

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.0346

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.137 AC: 20777 AN: 152210 Hom.: 2062 Cov.: 31 AF XY: 0.136 AC XY: 10153 AN XY: 74428

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.0662

Gnomad4 NFE AF: 0.0698

Gnomad4 OTH AF: 0.134

Alfa AF: 0.115 Hom.: 191

Bravo AF: 0.150

Asia WGS AF: 0.0930 AC: 325 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.74
Dann	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs28398457; hg19: chr8-95404375;