rs828701

Variant names:

• chr2-216126248-C-T
• rs828701
• NM_021141.4:c.798+217C>T

Variant summary

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

The NM_021141.4(XRCC5):​c.798+217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,994 control chromosomes in the GnomAD database, including 15,458 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 0.42 (15458 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.201
• Publications: 11 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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.798+217C>T		intron	N/A	NP_066964.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.798+217C>T		intron	N/A	ENSP00000375977.2
	XRCC5	ENST00000460284.5	TSL:1	n.1340+217C>T		intron	N/A
	XRCC5	ENST00000392133.7	TSL:5	c.798+217C>T		intron	N/A	ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64471 AN: 151876 Hom.: 15441 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.348

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.424 AC: 64505 AN: 151994 Hom.: 15458 Cov.: 32 AF XY: 0.421 AC XY: 31290 AN XY: 74260

African (AFR) AF: 0.216 AC: 8959 AN: 41478

American (AMR) AF: 0.350 AC: 5341 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1686 AN: 3464

East Asian (EAS) AF: 0.213 AC: 1104 AN: 5180

South Asian (SAS) AF: 0.538 AC: 2590 AN: 4810

European-Finnish (FIN) AF: 0.544 AC: 5726 AN: 10534

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37734 AN: 67956

Other (OTH) AF: 0.431 AC: 908 AN: 2106

Alfa AF: 0.526 Hom.: 11061

Bravo AF: 0.396

Asia WGS AF: 0.400 AC: 1392 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.2
DANN	Benign	0.80
PhyloP100		-0.20
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: rs828701; hg19: chr2-216990971;