rs7573191

Variant names:

• chr2-216199641-G-A
• rs7573191
• NM_021141.4:c.2109+4655G>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.2109+4655G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,964 control chromosomes in the GnomAD database, including 41,371 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 0.72 (41371 hom., cov: 30)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 4 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.2109+4655G>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.2109+4655G>A		intron_variant	Intron 19 of 20	1	NM_021141.4	ENSP00000375977.2
XRCC5	ENST00000460284.5	n.2651+4655G>A		intron_variant	Intron 16 of 17	1
XRCC5	ENST00000392133.7	c.2109+4655G>A		intron_variant	Intron 21 of 22	5		ENSP00000375978.3

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109943 AN: 151846 Hom.: 41305 Cov.: 30

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.762

Gnomad ASJ AF: 0.674

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.784

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.724 AC: 110067 AN: 151964 Hom.: 41371 Cov.: 30 AF XY: 0.731 AC XY: 54282 AN XY: 74248

African (AFR) AF: 0.906 AC: 37568 AN: 41484

American (AMR) AF: 0.763 AC: 11659 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.674 AC: 2335 AN: 3464

East Asian (EAS) AF: 0.946 AC: 4892 AN: 5170

South Asian (SAS) AF: 0.784 AC: 3773 AN: 4812

European-Finnish (FIN) AF: 0.662 AC: 6967 AN: 10528

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.599 AC: 40659 AN: 67918

Other (OTH) AF: 0.717 AC: 1512 AN: 2108

Alfa AF: 0.677 Hom.: 6073

Bravo AF: 0.741

Asia WGS AF: 0.846 AC: 2944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.010
DANN	Benign	0.44
PhyloP100		-2.2
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: rs7573191; hg19: chr2-217064364;