8-94378693-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.2248-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,144,010 control chromosomes in the GnomAD database, including 87,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12471 hom., cov: 32)
  • Exomes 𝑓: 0.38 (74859 hom.)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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=-0.92).
• BP6: Variant 8-94378693-C-T is Benign according to our data. Variant chr8-94378693-C-T is described in ClinVar as [Benign]. Clinvar id is 1252579.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD54B	NM_012415.3	c.2248-59G>A		intron_variant		ENST00000336148.10
RAD54B	NM_001205263.2	c.1696-59G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD54B	ENST00000336148.10	c.2248-59G>A		intron_variant		1	NM_012415.3	P1
FSBP	ENST00000517506.2	c.*1928-59G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61160 AN: 151860 Hom.: 12462 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.312

Gnomad AMR AF: 0.510

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.434

GnomAD4 exome AF: 0.383 AC: 380127 AN: 992032 Hom.: 74859 AF XY: 0.384 AC XY: 195443 AN XY: 509444

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.577

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.467

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.420

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.386

GnomAD4 genome AF: 0.403 AC: 61205 AN: 151978 Hom.: 12471 Cov.: 32 AF XY: 0.409 AC XY: 30404 AN XY: 74282

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.431

Alfa AF: 0.388 Hom.: 2327

Bravo AF: 0.412

Asia WGS AF: 0.421 AC: 1465 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	-0.92
Cadd	Benign	1.3
Dann	Benign	0.24

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: rs716770; hg19: chr8-95390921; COSMIC: COSV60251206; COSMIC: COSV60251206;