NM_021141.4:c.136-196G>A

Variant names:

• chr2-216116463-G-A
• rs705649
• NM_021141.4:c.136-196G>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.136-196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,908 control chromosomes in the GnomAD database, including 20,840 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 0.52 (20840 hom., cov: 31)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.136-196G>A		intron_variant	Intron 2 of 20	ENST00000392132.7	NP_066964.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
XRCC5	ENST00000392132.7	c.136-196G>A		intron_variant	Intron 2 of 20	1	NM_021141.4	ENSP00000375977.2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78643 AN: 151790 Hom.: 20806 Cov.: 31

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.558

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.518 AC: 78715 AN: 151908 Hom.: 20840 Cov.: 31 AF XY: 0.511 AC XY: 37981 AN XY: 74282

African (AFR) AF: 0.538 AC: 22292 AN: 41410

American (AMR) AF: 0.387 AC: 5907 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1686 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1104 AN: 5168

South Asian (SAS) AF: 0.538 AC: 2592 AN: 4814

European-Finnish (FIN) AF: 0.544 AC: 5723 AN: 10528

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.558 AC: 37900 AN: 67942

Other (OTH) AF: 0.495 AC: 1042 AN: 2104

Alfa AF: 0.525 Hom.: 6982

Bravo AF: 0.503

Asia WGS AF: 0.419 AC: 1460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.67
PhyloP100		-0.11
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs705649; hg19: chr2-216981186;