8-94386817-C-T

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.1985+167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 152,210 control chromosomes in the GnomAD database, including 62,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.91 (62774 hom., cov: 33)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0780

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=-0.83).
• BP6: Variant 8-94386817-C-T is Benign according to our data. Variant chr8-94386817-C-T is described in ClinVar as [Benign]. Clinvar id is 1259423.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54B	NM_012415.3	c.1985+167G>A		intron_variant		ENST00000336148.10
RAD54B	NM_001205263.2	c.1433+167G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54B	ENST00000336148.10	c.1985+167G>A		intron_variant		1	NM_012415.3	P1
FSBP	ENST00000517506.2	c.*1665+167G>A		intron_variant, NMD_transcript_variant		5
RAD54B	ENST00000518358.1	n.446+167G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.905 AC: 137649 AN: 152092 Hom.: 62728 Cov.: 33

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.890

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.972

Gnomad MID AF: 0.896

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.905 AC: 137752 AN: 152210 Hom.: 62774 Cov.: 33 AF XY: 0.905 AC XY: 67348 AN XY: 74448

Gnomad4 AFR AF: 0.822

Gnomad4 AMR AF: 0.934

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.972

Gnomad4 NFE AF: 0.958

Gnomad4 OTH AF: 0.920

Alfa AF: 0.935 Hom.: 7335

Bravo AF: 0.898

Asia WGS AF: 0.787 AC: 2733 AN: 3470

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.58

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: rs2470741; hg19: chr8-95399045;