5-83249721-T-TAATC

Position:

• chr5-83249721-T-TAATC

Variant summary

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

The NM_003401.5(XRCC4):​c.746-8807_746-8804dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (14116 hom., cov: 0)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.695

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 (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC4	NM_003401.5	c.746-8807_746-8804dup		intron_variant		ENST00000396027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC4	ENST00000396027.9	c.746-8807_746-8804dup		intron_variant		5	NM_003401.5	A1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57796 AN: 151376 Hom.: 14073 Cov.: 0

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.363

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

GnomAD4 genome AF: 0.382 AC: 57904 AN: 151494 Hom.: 14116 Cov.: 0 AF XY: 0.387 AC XY: 28613 AN XY: 74010

Gnomad4 AFR AF: 0.648

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.243

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.370

Alfa AF: 0.305 Hom.: 1138

Bravo AF: 0.404

Asia WGS AF: 0.533 AC: 1847 AN: 3470

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: rs1611026; hg19: chr5-82545540;