rs3834

Variant names:

• chr2-216201980-G-A
• rs3834
• NM_021141.4:c.2110-2342G>A

Variant summary

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

The NM_021141.4(XRCC5):​c.2110-2342G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,158 control chromosomes in the GnomAD database, including 2,498 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 0.16 (2498 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.75
• Publications: 10 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	NM_021141.4	MANE Select	c.2110-2342G>A		intron	N/A	NP_066964.1	P13010

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XRCC5	ENST00000392132.7	TSL:1 MANE Select	c.2110-2342G>A		intron	N/A	ENSP00000375977.2	P13010
	XRCC5	ENST00000460284.5	TSL:1	n.2652-2342G>A		intron	N/A
	XRCC5	ENST00000947464.1		c.2176-2342G>A		intron	N/A	ENSP00000617523.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24904 AN: 152040 Hom.: 2491 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.164 AC: 24953 AN: 152158 Hom.: 2498 Cov.: 32 AF XY: 0.164 AC XY: 12226 AN XY: 74400

African (AFR) AF: 0.281 AC: 11635 AN: 41466

American (AMR) AF: 0.116 AC: 1768 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 476 AN: 3470

East Asian (EAS) AF: 0.0720 AC: 373 AN: 5180

South Asian (SAS) AF: 0.173 AC: 836 AN: 4826

European-Finnish (FIN) AF: 0.113 AC: 1201 AN: 10592

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8289 AN: 68008

Other (OTH) AF: 0.136 AC: 287 AN: 2114

Alfa AF: 0.132 Hom.: 1036

Bravo AF: 0.168

Asia WGS AF: 0.137 AC: 474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.0
DANN	Benign	0.53
PhyloP100		-2.7
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: rs3834; hg19: chr2-217066703;