ENST00000487861.5:c.1037-43041C>T

Variant names:

• chr14-68567965-C-T
• rs999737
• ENST00000487861.5:c.1037-43041C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000487861.5(RAD51B):​c.1037-43041C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,064 control chromosomes in the GnomAD database, including 2,501 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.16 (2501 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0830
• Publications: 152 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-68567965-C-T is Benign according to our data. Variant chr14-68567965-C-T is described in ClinVar as Benign. ClinVar VariationId is 225822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000487861.5. 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_001321821.2		c.1037-43041C>T		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.1037-26520C>T		intron	N/A	NP_598193.2
	RAD51B	NM_001321809.2		c.1037-34698C>T		intron	N/A	NP_001308738.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1037-43041C>T		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1037-26520C>T		intron	N/A	ENSP00000419471.1
	RAD51B	ENST00000488612.5	TSL:1	c.1037-82816C>T		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24103 AN: 151946 Hom.: 2502 Cov.: 32

Gnomad AFR AF: 0.0443

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.126

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.159 AC: 24112 AN: 152064 Hom.: 2501 Cov.: 32 AF XY: 0.156 AC XY: 11627 AN XY: 74306

African (AFR) AF: 0.0442 AC: 1833 AN: 41484

American (AMR) AF: 0.166 AC: 2531 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.126 AC: 436 AN: 3470

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5172

South Asian (SAS) AF: 0.128 AC: 616 AN: 4806

European-Finnish (FIN) AF: 0.193 AC: 2037 AN: 10570

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16071 AN: 67972

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.207 Hom.: 16167

Bravo AF: 0.150

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.083
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: rs999737; hg19: chr14-69034682;