rs3770521

Variant names:

• chr2-216115437-G-A
• rs3770521
• NM_021141.4:c.136-1222G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-216115437-G-A
• chr2-216115437-G-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.136-1222G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,060 control chromosomes in the GnomAD database, including 7,620 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 0.30 (7620 hom., cov: 32)
• Consequence: XRCC5 NM_021141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
XRCC5	NM_021141.4	c.136-1222G>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.136-1222G>A		intron_variant	Intron 2 of 20	1	NM_021141.4	ENSP00000375977.2

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45700 AN: 151942 Hom.: 7608 Cov.: 32

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.460

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.301 AC: 45722 AN: 152060 Hom.: 7620 Cov.: 32 AF XY: 0.307 AC XY: 22860 AN XY: 74346

African (AFR) AF: 0.230 AC: 9540 AN: 41468

American (AMR) AF: 0.461 AC: 7048 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1129 AN: 3470

East Asian (EAS) AF: 0.666 AC: 3444 AN: 5168

South Asian (SAS) AF: 0.228 AC: 1100 AN: 4824

European-Finnish (FIN) AF: 0.352 AC: 3712 AN: 10556

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18680 AN: 67974

Other (OTH) AF: 0.325 AC: 685 AN: 2106

Alfa AF: 0.306 Hom.: 1211

Bravo AF: 0.315

Asia WGS AF: 0.387 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.50
PhyloP100		0.011
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: rs3770521; hg19: chr2-216980160;