14-68567965-C-T

Position:

• chr14-68567965-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51B	NM_001321809.2	c.1037-34698C>T		intron_variant			NP_001308738.1
RAD51B	NM_001321810.2	c.1037-34698C>T		intron_variant			NP_001308739.1
RAD51B	NM_001321815.1	c.923-43193C>T		intron_variant			NP_001308744.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51B	ENST00000487270.5	c.1037-26520C>T		intron_variant		1		ENSP00000419471
RAD51B	ENST00000487861.5	c.1037-43041C>T		intron_variant		1		ENSP00000419881
RAD51B	ENST00000488612.5	c.1037-82816C>T		intron_variant		1		ENSP00000420061

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

Gnomad4 AFR AF: 0.0442

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.126

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.236

Gnomad4 OTH AF: 0.152

Alfa AF: 0.214 Hom.: 8716

Bravo AF: 0.150

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs999737; hg19: chr14-69034682;