rs3821107

Variant names:

• chr2-216166605-T-C
• rs3821107
• NM_021141.4:c.1834+4557T>C

Variant summary

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

The NM_021141.4(XRCC5):​c.1834+4557T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,098 control chromosomes in the GnomAD database, including 7,410 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 0.29 (7410 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 8 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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.1834+4557T>C		intron_variant	Intron 16 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.1834+4557T>C		intron_variant	Intron 16 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2376+4557T>C		intron_variant	Intron 13 of 17	1
XRCC5	ENST00000392133.7	c.1834+4557T>C		intron_variant	Intron 18 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44715 AN: 151980 Hom.: 7398 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.294 AC: 44774 AN: 152098 Hom.: 7410 Cov.: 32 AF XY: 0.294 AC XY: 21888 AN XY: 74362

African (AFR) AF: 0.443 AC: 18359 AN: 41440

American (AMR) AF: 0.201 AC: 3077 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3470

East Asian (EAS) AF: 0.233 AC: 1205 AN: 5180

South Asian (SAS) AF: 0.461 AC: 2222 AN: 4822

European-Finnish (FIN) AF: 0.233 AC: 2468 AN: 10580

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.231 AC: 15693 AN: 68002

Other (OTH) AF: 0.248 AC: 525 AN: 2116

Alfa AF: 0.249 Hom.: 20757

Bravo AF: 0.293

Asia WGS AF: 0.357 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.71
DANN	Benign	0.32
PhyloP100		-1.0
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: rs3821107; hg19: chr2-217031328;