ENST00000487861.5:c.1036+51190C>T

Variant names:

• chr14-68519440-C-T
• rs11624164
• ENST00000487861.5:c.1036+51190C>T

Variant summary

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

The ENST00000487861.5(RAD51B):​c.1036+51190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,124 control chromosomes in the GnomAD database, including 3,154 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 0.18 (3154 hom., cov: 32)
• Consequence: RAD51B ENST00000487861.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194
• Publications: 16 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC124903334	XR_007064222.1	n.17991G>A		non_coding_transcript_exon_variant	Exon 2 of 2
LOC124903334	XR_007064223.1	n.17798G>A		non_coding_transcript_exon_variant	Exon 3 of 3
RAD51B	NM_001321821.2	c.1036+51190C>T		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.1036+51190C>T		intron_variant	Intron 10 of 10	1		ENSP00000419881.1
RAD51B	ENST00000487270.5	c.1036+51190C>T		intron_variant	Intron 10 of 10	1		ENSP00000419471.1
RAD51B	ENST00000488612.5	c.1036+51190C>T		intron_variant	Intron 10 of 11	1		ENSP00000420061.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27380 AN: 152006 Hom.: 3156 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0654

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.180 AC: 27385 AN: 152124 Hom.: 3154 Cov.: 32 AF XY: 0.180 AC XY: 13353 AN XY: 74384

African (AFR) AF: 0.0496 AC: 2058 AN: 41510

American (AMR) AF: 0.180 AC: 2754 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 477 AN: 3464

East Asian (EAS) AF: 0.0658 AC: 341 AN: 5186

South Asian (SAS) AF: 0.172 AC: 831 AN: 4822

European-Finnish (FIN) AF: 0.236 AC: 2499 AN: 10576

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.262 AC: 17819 AN: 67966

Other (OTH) AF: 0.163 AC: 345 AN: 2112

Alfa AF: 0.206 Hom.: 4851

Bravo AF: 0.168

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	14
DANN	Benign	0.68
PhyloP100		0.19
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: rs11624164; hg19: chr14-68986157;