rs2180611

chr14-68653768-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000488612.5(RAD51B):c.*11+2912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 152,152 control chromosomes in the GnomAD database, including 11,848 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 0.38 (11848 hom., cov: 33)
• Consequence: RAD51B ENST00000488612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.455

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]

LOC124903333 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124903333	XR_007064220.1	n.189-1100G>A		intron_variant, non_coding_transcript_variant
RAD51B	NM_001321818.2	c.1037-29169C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51B	ENST00000488612.5	c.*11+2912C>T		intron_variant		1
RAD51B	ENST00000478014.5	n.384-29169C>T		intron_variant, non_coding_transcript_variant		3
RAD51B	ENST00000553595.5	n.614-29169C>T		intron_variant, non_coding_transcript_variant		3
RAD51B	ENST00000554244.5	n.488-29169C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57900 AN: 152034 Hom.: 11844 Cov.: 33

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.558

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.381 AC: 57916 AN: 152152 Hom.: 11848 Cov.: 33 AF XY: 0.389 AC XY: 28941 AN XY: 74400

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.460

Gnomad4 ASJ AF: 0.496

Gnomad4 EAS AF: 0.767

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.362

Gnomad4 OTH AF: 0.400

Alfa AF: 0.382 Hom.: 22340

Bravo AF: 0.382

Asia WGS AF: 0.609 AC: 2113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.56
Dann	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2180611; hg19: chr14-69120485;