ENST00000487861.5:c.1037-47071C>A

Variant names:

• chr14-68563935-C-A
• rs17105852
• ENST00000487861.5:c.1037-47071C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000487861.5(RAD51B):​c.1037-47071C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 982,132 control chromosomes in the GnomAD database, including 648 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 0.044 (180 hom., cov: 33)
  • Exomes 𝑓: 0.032 (468 hom.)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 11 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903335	XR_007064224.1	n.1316G>T		non_coding_transcript_exon_variant	Exon 1 of 2
LOC124903335	XR_007064226.1	n.1316G>T		non_coding_transcript_exon_variant	Exon 1 of 3
RAD51B	NM_001321821.2	c.1037-47071C>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.1037-47071C>A		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1037-30550C>A		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1037-86846C>A		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6667 AN: 152210 Hom.: 179 Cov.: 33

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0363

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0317 AC: 26314 AN: 829804 Hom.: 468 Cov.: 28 AF XY: 0.0317 AC XY: 12169 AN XY: 383322

African (AFR) AF: 0.0669 AC: 1050 AN: 15706

American (AMR) AF: 0.0286 AC: 28 AN: 980

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 287 AN: 5134

East Asian (EAS) AF: 0.00 AC: 0 AN: 3614

South Asian (SAS) AF: 0.0250 AC: 410 AN: 16380

European-Finnish (FIN) AF: 0.0145 AC: 4 AN: 276

Middle Eastern (MID) AF: 0.0451 AC: 73 AN: 1620

European-Non Finnish (NFE) AF: 0.0311 AC: 23564 AN: 758904

Other (OTH) AF: 0.0330 AC: 898 AN: 27190

GnomAD4 genome AF: 0.0438 AC: 6677 AN: 152328 Hom.: 180 Cov.: 33 AF XY: 0.0431 AC XY: 3213 AN XY: 74486

African (AFR) AF: 0.0702 AC: 2918 AN: 41554

American (AMR) AF: 0.0362 AC: 554 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3470

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4828

European-Finnish (FIN) AF: 0.0258 AC: 274 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0364 AC: 2477 AN: 68042

Other (OTH) AF: 0.0383 AC: 81 AN: 2116

Alfa AF: 0.0207 Hom.: 10

Bravo AF: 0.0455

Asia WGS AF: 0.0190 AC: 67 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	16
DANN	Benign	0.86
PhyloP100		0.18
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: rs17105852; hg19: chr14-69030652;