chr14-68333883-T-C

Variant names:

• chr14-68333883-T-C
• rs4902567
• NM_133510.4:c.853+41903T>C

Variant summary

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

The NM_001321821.2(RAD51B):​c.853+41903T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,094 control chromosomes in the GnomAD database, including 56,355 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 0.86 (56355 hom., cov: 30)
• Consequence: RAD51B NM_001321821.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.928
• Publications: 4 publications found

Genes affected

RAD51B (HGNC:9822): (RAD51 paralog B) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are evolutionarily conserved proteins essential for DNA repair by homologous recombination. This protein has been shown to form a stable heterodimer with the family member RAD51C, which further interacts with the other family members, such as RAD51, XRCC2, and XRCC3. Overexpression of this gene was found to cause cell cycle G1 delay and cell apoptosis, which suggested a role of this protein in sensing DNA damage. Rearrangements between this locus and high mobility group AT-hook 2 (HMGA2, GeneID 8091) have been observed in uterine leiomyomata. [provided by RefSeq, Mar 2016]

RAD51B Gene-Disease associations (from GenCC):

• primary ovarian failure

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321821.2. 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
	RAD51B	NM_133510.4	MANE Select	c.853+41903T>C		intron	N/A	NP_598194.1
	RAD51B	NM_001321821.2		c.853+41903T>C		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.853+41903T>C		intron	N/A	NP_598193.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000471583.6	TSL:1 MANE Select	c.853+41903T>C		intron	N/A	ENSP00000418859.1
	RAD51B	ENST00000487861.5	TSL:1	c.853+41903T>C		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.853+41903T>C		intron	N/A	ENSP00000419471.1

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130238 AN: 151976 Hom.: 56284 Cov.: 30

Gnomad AFR AF: 0.963

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.848

Gnomad ASJ AF: 0.718

Gnomad EAS AF: 0.991

Gnomad SAS AF: 0.848

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.820

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

GnomAD4 genome AF: 0.857 AC: 130369 AN: 152094 Hom.: 56355 Cov.: 30 AF XY: 0.856 AC XY: 63615 AN XY: 74340

African (AFR) AF: 0.963 AC: 39978 AN: 41498

American (AMR) AF: 0.849 AC: 12957 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 2490 AN: 3466

East Asian (EAS) AF: 0.991 AC: 5137 AN: 5184

South Asian (SAS) AF: 0.849 AC: 4091 AN: 4818

European-Finnish (FIN) AF: 0.781 AC: 8247 AN: 10560

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54789 AN: 67978

Other (OTH) AF: 0.822 AC: 1738 AN: 2114

Alfa AF: 0.816 Hom.: 24723

Bravo AF: 0.866

Asia WGS AF: 0.903 AC: 3141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.3
DANN	Benign	0.72
PhyloP100		-0.93
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: rs4902567; hg19: chr14-68800600;