8-94387390-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.1810-231G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 345,126 control chromosomes in the GnomAD database, including 26,438 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.39 (11521 hom., cov: 32)
  • Exomes 𝑓: 0.39 (14917 hom.)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

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=-0.88).
• BP6: Variant 8-94387390-C-T is Benign according to our data. Variant chr8-94387390-C-T is described in ClinVar as [Benign]. Clinvar id is 1290502.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54B	NM_012415.3	c.1810-231G>A		intron_variant		ENST00000336148.10
RAD54B	NM_001205263.2	c.1258-231G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54B	ENST00000336148.10	c.1810-231G>A		intron_variant		1	NM_012415.3	P1
RAD54B	ENST00000518358.1	n.40G>A		non_coding_transcript_exon_variant	1/2	3
FSBP	ENST00000517506.2	c.*1490-231G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58720 AN: 151848 Hom.: 11518 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.418

GnomAD4 exome AF: 0.390 AC: 75412 AN: 193160 Hom.: 14917 Cov.: 2 AF XY: 0.391 AC XY: 38597 AN XY: 98796

Gnomad4 AFR exome AF: 0.369

Gnomad4 AMR exome AF: 0.533

Gnomad4 ASJ exome AF: 0.390

Gnomad4 EAS exome AF: 0.473

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.430

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.387

GnomAD4 genome AF: 0.387 AC: 58755 AN: 151966 Hom.: 11521 Cov.: 32 AF XY: 0.393 AC XY: 29210 AN XY: 74264

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.468

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.372

Gnomad4 OTH AF: 0.414

Alfa AF: 0.384 Hom.: 1858

Bravo AF: 0.393

Asia WGS AF: 0.420 AC: 1461 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	2.6
Dann	Benign	0.77

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: rs16916788; hg19: chr8-95399618; COSMIC: COSV60250895; COSMIC: COSV60250895;