chr8-94438023-T-C

Variant names:

• chr8-94438023-T-C
• rs3136403
• NM_012415.3:c.304+20245A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012415.3(RAD54B):​c.304+20245A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 152,184 control chromosomes in the GnomAD database, including 1,535 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (1535 hom., cov: 32)
• Consequence: RAD54B NM_012415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 2 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54B	NM_012415.3	MANE Select	c.304+20245A>G		intron	N/A	NP_036547.1
	RAD54B	NM_001205262.3		c.305-5367A>G		intron	N/A	NP_001192191.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD54B	ENST00000336148.10	TSL:1 MANE Select	c.304+20245A>G		intron	N/A	ENSP00000336606.5
	RAD54B	ENST00000463267.5	TSL:1	n.305-5367A>G		intron	N/A	ENSP00000430808.1
	RAD54B	ENST00000523839.5	TSL:3	c.304+20245A>G		intron	N/A	ENSP00000428554.1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15693 AN: 152066 Hom.: 1530 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.0518

Gnomad EAS AF: 0.0343

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0263

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.103 AC: 15719 AN: 152184 Hom.: 1535 Cov.: 32 AF XY: 0.104 AC XY: 7772 AN XY: 74410

African (AFR) AF: 0.246 AC: 10214 AN: 41484

American (AMR) AF: 0.155 AC: 2371 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0518 AC: 180 AN: 3472

East Asian (EAS) AF: 0.0344 AC: 178 AN: 5180

South Asian (SAS) AF: 0.0907 AC: 437 AN: 4820

European-Finnish (FIN) AF: 0.0254 AC: 269 AN: 10600

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0263 AC: 1789 AN: 68016

Other (OTH) AF: 0.101 AC: 213 AN: 2116

Alfa AF: 0.0688 Hom.: 171

Bravo AF: 0.118

Asia WGS AF: 0.0800 AC: 279 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.19
PhyloP100		0.077
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: rs3136403; hg19: chr8-95450251;