chr5-83225799-C-A

Position:

• chr5-83225799-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003401.5(XRCC4):​c.745+20878C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 151,242 control chromosomes in the GnomAD database, including 9,776 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 0.27 (9776 hom., cov: 30)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.620

Genes affected

XRCC4 (HGNC:12831): (X-ray repair cross complementing 4) The protein encoded by this gene functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand breaks. This protein plays a role in both non-homologous end joining and the completion of V(D)J recombination. Mutations in this gene can cause short stature, microcephaly, and endocrine dysfunction (SSMED). Alternate transcript variants such as NM_022406 are unlikely to be expressed in some individuals due to a polymorphism (rs1805377) in the last splice acceptor site. [provided by RefSeq, Oct 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XRCC4	NM_003401.5	c.745+20878C>A		intron_variant		ENST00000396027.9	NP_003392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
XRCC4	ENST00000396027.9	c.745+20878C>A		intron_variant		5	NM_003401.5	ENSP00000379344	A1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40542 AN: 151124 Hom.: 9750 Cov.: 30

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.649

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0689

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.269 AC: 40623 AN: 151242 Hom.: 9776 Cov.: 30 AF XY: 0.273 AC XY: 20135 AN XY: 73794

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.649

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.128

Gnomad4 NFE AF: 0.0689

Gnomad4 OTH AF: 0.242

Alfa AF: 0.0976 Hom.: 2607

Bravo AF: 0.298

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.94
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs7711825; hg19: chr5-82521618;