rs828907

Variant names:

• chr2-216108009-G-T
• rs828907
• ENST00000392133.7:c.-347+311G>T

Variant summary

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

The ENST00000392133.7(XRCC5):​c.-347+311G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,118 control chromosomes in the GnomAD database, including 11,596 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 0.37 (11596 hom., cov: 32)
• Consequence: XRCC5 ENST00000392133.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 32 publications found

Genes affected

XRCC5 (HGNC:12833): (X-ray repair cross complementing 5) The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392133.7	c.-347+311G>T		intron_variant	Intron 2 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56509 AN: 151998 Hom.: 11585 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.372 AC: 56532 AN: 152118 Hom.: 11596 Cov.: 32 AF XY: 0.371 AC XY: 27589 AN XY: 74354

African (AFR) AF: 0.221 AC: 9173 AN: 41518

American (AMR) AF: 0.291 AC: 4445 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.449 AC: 1556 AN: 3468

East Asian (EAS) AF: 0.209 AC: 1083 AN: 5170

South Asian (SAS) AF: 0.527 AC: 2540 AN: 4822

European-Finnish (FIN) AF: 0.456 AC: 4810 AN: 10556

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31784 AN: 67984

Other (OTH) AF: 0.388 AC: 816 AN: 2104

Alfa AF: 0.433 Hom.: 55639

Bravo AF: 0.347

Asia WGS AF: 0.395 AC: 1374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.61
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs828907; hg19: chr2-216972732;