chr14-68604431-T-C

Variant names:

• chr14-68604431-T-C
• rs2236184
• ENST00000487861.5:c.1037-6575T>C

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1037-6575T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.71 in 152,124 control chromosomes in the GnomAD database, including 38,489 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 0.71 (38489 hom., cov: 33)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51B	NM_001321821.2	c.1037-6575T>C		intron_variant	Intron 10 of 10		NP_001308750.1
RAD51B	NM_001321809.2	c.*33+1728T>C		intron_variant	Intron 11 of 11		NP_001308738.1
RAD51B	NM_001321818.2	c.1037-78506T>C		intron_variant	Intron 10 of 10		NP_001308747.1
RAD51B	NM_001321815.1	c.923-6727T>C		intron_variant	Intron 9 of 9		NP_001308744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487861.5	c.1037-6575T>C		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000488612.5	c.1037-46350T>C		intron_variant	Intron 10 of 11	1		ENSP00000420061.1
RAD51B	ENST00000478014.5	n.384-78506T>C		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.710 AC: 107952 AN: 152006 Hom.: 38462 Cov.: 33

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.687

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.710 AC: 108029 AN: 152124 Hom.: 38489 Cov.: 33 AF XY: 0.709 AC XY: 52746 AN XY: 74366

African (AFR) AF: 0.757 AC: 31421 AN: 41520

American (AMR) AF: 0.686 AC: 10492 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2674 AN: 3472

East Asian (EAS) AF: 0.739 AC: 3803 AN: 5148

South Asian (SAS) AF: 0.788 AC: 3807 AN: 4830

European-Finnish (FIN) AF: 0.611 AC: 6469 AN: 10584

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.692 AC: 47008 AN: 67958

Other (OTH) AF: 0.726 AC: 1534 AN: 2112

Alfa AF: 0.700 Hom.: 73502

Bravo AF: 0.714

Asia WGS AF: 0.739 AC: 2573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.24
PhyloP100		-1.2
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: rs2236184; hg19: chr14-69071148; COSMIC: COSV66852820;