14-68536271-A-G

Variant names:

• chr14-68536271-A-G
• rs2189517
• ENST00000487861.5:c.1036+68021A>G

Variant summary

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

The XR_007064222.1(LOC124903334):​n.1234T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 152,050 control chromosomes in the GnomAD database, including 19,091 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 0.49 (19091 hom., cov: 32)
• Consequence: LOC124903334 XR_007064222.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.719
• Publications: 14 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

LOC124903334 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 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.1036+68021A>G		intron	N/A	NP_001308750.1
	RAD51B	NM_133509.5		c.1037-58214A>G		intron	N/A	NP_598193.2
	RAD51B	NM_001321812.1		c.1037-3929A>G		intron	N/A	NP_001308741.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51B	ENST00000487861.5	TSL:1	c.1036+68021A>G		intron	N/A	ENSP00000419881.1
	RAD51B	ENST00000487270.5	TSL:1	c.1037-58214A>G		intron	N/A	ENSP00000419471.1
	RAD51B	ENST00000488612.5	TSL:1	c.1036+68021A>G		intron	N/A	ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.490 AC: 74462 AN: 151932 Hom.: 19078 Cov.: 32

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.505

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.490 AC: 74499 AN: 152050 Hom.: 19091 Cov.: 32 AF XY: 0.489 AC XY: 36332 AN XY: 74318

African (AFR) AF: 0.326 AC: 13530 AN: 41500

American (AMR) AF: 0.533 AC: 8148 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.505 AC: 1752 AN: 3468

East Asian (EAS) AF: 0.697 AC: 3608 AN: 5174

South Asian (SAS) AF: 0.496 AC: 2390 AN: 4818

European-Finnish (FIN) AF: 0.502 AC: 5282 AN: 10532

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38236 AN: 67954

Other (OTH) AF: 0.493 AC: 1041 AN: 2110

Alfa AF: 0.545 Hom.: 86970

Bravo AF: 0.490

Asia WGS AF: 0.559 AC: 1947 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.1
DANN	Benign	0.34
PhyloP100		0.72
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: rs2189517; hg19: chr14-69002988;