rs1468280

Variant names:

• chr14-68565143-G-A
• rs1468280
• ENST00000487861.5:c.1037-45863G>A

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-45863G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,914 control chromosomes in the GnomAD database, including 18,241 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 0.48 (18241 hom., cov: 33)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200
• Publications: 3 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

LOC124903335 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903335	XR_007064224.1	n.108C>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903335	XR_007064226.1	n.108C>T		non_coding_transcript_exon_variant	Exon 1 of 3
RAD51B	NM_001321821.2	c.1037-45863G>A		intron_variant	Intron 10 of 10		NP_001308750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-45863G>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-29342G>A		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-85638G>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72927 AN: 151796 Hom.: 18229 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.503

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.539

Gnomad FIN AF: 0.623

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.480 AC: 72965 AN: 151914 Hom.: 18241 Cov.: 33 AF XY: 0.487 AC XY: 36141 AN XY: 74244

African (AFR) AF: 0.335 AC: 13889 AN: 41432

American (AMR) AF: 0.526 AC: 8038 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.503 AC: 1744 AN: 3470

East Asian (EAS) AF: 0.588 AC: 3033 AN: 5154

South Asian (SAS) AF: 0.539 AC: 2596 AN: 4814

European-Finnish (FIN) AF: 0.623 AC: 6561 AN: 10536

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

European-Non Finnish (NFE) AF: 0.522 AC: 35455 AN: 67916

Other (OTH) AF: 0.482 AC: 1016 AN: 2106

Alfa AF: 0.518 Hom.: 8955

Bravo AF: 0.467

Asia WGS AF: 0.591 AC: 2055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		-0.20
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1468280; hg19: chr14-69031860;