rs3835

Variant names:

• chr2-216201914-G-A
• rs3835
• NM_021141.4:c.2110-2408G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-216201914-G-A
• chr2-216201914-G-C
• chr2-216201914-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021141.4(XRCC5):​c.2110-2408G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,168 control chromosomes in the GnomAD database, including 4,611 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 0.21 (4611 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 24 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.419 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.2110-2408G>A		intron_variant	Intron 19 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.2110-2408G>A		intron_variant	Intron 19 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2652-2408G>A		intron_variant	Intron 16 of 17	1
XRCC5	ENST00000392133.7	c.2110-2408G>A		intron_variant	Intron 21 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31148 AN: 152050 Hom.: 4587 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0718

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.163

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

GnomAD4 genome AF: 0.205 AC: 31231 AN: 152168 Hom.: 4611 Cov.: 32 AF XY: 0.204 AC XY: 15192 AN XY: 74418

African (AFR) AF: 0.424 AC: 17585 AN: 41464

American (AMR) AF: 0.132 AC: 2017 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 474 AN: 3472

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5182

South Asian (SAS) AF: 0.173 AC: 835 AN: 4828

European-Finnish (FIN) AF: 0.113 AC: 1200 AN: 10602

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8314 AN: 68008

Other (OTH) AF: 0.161 AC: 341 AN: 2112

Alfa AF: 0.140 Hom.: 929

Bravo AF: 0.215

Asia WGS AF: 0.149 AC: 519 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	19
DANN	Benign	0.74
PhyloP100		1.4
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: rs3835; hg19: chr2-217066637;