8-94378693-C-T

Variant names:

• chr8-94378693-C-T
• rs716770
• NM_012415.3:c.2248-59G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1252579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 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.2248-59G>A		intron	N/A	NP_036547.1	Q9Y620-1
	RAD54B	NM_001205263.2		c.1696-59G>A		intron	N/A	NP_001192192.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54B	ENST00000336148.10	TSL:1 MANE Select	c.2248-59G>A		intron	N/A	ENSP00000336606.5	Q9Y620-1
	RAD54B	ENST00000911517.1		c.2248-59G>A		intron	N/A	ENSP00000581576.1
	RAD54B	ENST00000911516.1		c.2248-59G>A		intron	N/A	ENSP00000581575.1

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

African (AFR) AF: 0.417 AC: 9365 AN: 22452

American (AMR) AF: 0.577 AC: 16907 AN: 29310

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 8048 AN: 20238

East Asian (EAS) AF: 0.467 AC: 17294 AN: 37024

South Asian (SAS) AF: 0.416 AC: 28466 AN: 68370

European-Finnish (FIN) AF: 0.420 AC: 20872 AN: 49720

Middle Eastern (MID) AF: 0.421 AC: 1993 AN: 4732

European-Non Finnish (NFE) AF: 0.363 AC: 260195 AN: 716226

Other (OTH) AF: 0.386 AC: 16987 AN: 43960

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

African (AFR) AF: 0.404 AC: 16728 AN: 41444

American (AMR) AF: 0.510 AC: 7791 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1363 AN: 3470

East Asian (EAS) AF: 0.467 AC: 2414 AN: 5168

South Asian (SAS) AF: 0.423 AC: 2034 AN: 4804

European-Finnish (FIN) AF: 0.410 AC: 4324 AN: 10546

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25235 AN: 67974

Other (OTH) AF: 0.431 AC: 903 AN: 2096

Alfa AF: 0.389 Hom.: 2396

Bravo AF: 0.412

Asia WGS AF: 0.421 AC: 1465 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.3
DANN	Benign	0.24
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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