rs28360071

chr5-83142292-GGATGAGGAAACTAACTCTCAGTGGTGTTTA-Gchr5-83142292-GGATGAGGAAACTAACTCTCAGTGGTGTTTA-GGATGAGGAAACTAACTCTCAGTGGTGTTTAGATGAGGAAACTAACTCTCAGTGGTGTTTA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003401.5(XRCC4):c.315+31120_315+31149del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 150,308 control chromosomes in the GnomAD database, including 18,197 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.48 (18197 hom., cov: 0)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC4	NM_003401.5	c.315+31120_315+31149del		intron_variant		ENST00000396027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC4	ENST00000396027.9	c.315+31120_315+31149del		intron_variant		5	NM_003401.5	A1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72075 AN: 150198 Hom.: 18182 Cov.: 0

Gnomad AFR AF: 0.626

Gnomad AMI AF: 0.506

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.480 AC: 72117 AN: 150308 Hom.: 18197 Cov.: 0 AF XY: 0.479 AC XY: 35135 AN XY: 73372

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.339

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.480

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.446

Alfa AF: 0.464 Hom.: 1847

Asia WGS AF: 0.372 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28360071; hg19: chr5-82438111;