rs28360317

chr5-83323739-A-ACTC

Variant summary

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

The NM_003401.5(XRCC4):c.894-29390_894-29389insCCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 151,744 control chromosomes in the GnomAD database, including 7,490 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.24 (7490 hom., cov: 27)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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 = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC4	NM_003401.5	c.894-29390_894-29389insCCT		intron_variant		ENST00000396027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC4	ENST00000396027.9	c.894-29390_894-29389insCCT		intron_variant		5	NM_003401.5	A1
XRCC4	ENST00000282268.7	c.894-29390_894-29389insCCT		intron_variant		1		A1
XRCC4	ENST00000511817.1	c.894-29384_894-29383insCCT		intron_variant		1		P3
XRCC4	ENST00000338635.10	c.894-29384_894-29383insCCT		intron_variant		2		P3

Frequencies

GnomAD3 genomes AF: 0.244 AC: 36953 AN: 151626 Hom.: 7451 Cov.: 27

Gnomad AFR AF: 0.493

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.288

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.708

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0795

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.244 AC: 37043 AN: 151744 Hom.: 7490 Cov.: 27 AF XY: 0.247 AC XY: 18336 AN XY: 74152

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.288

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.708

Gnomad4 SAS AF: 0.159

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0795

Gnomad4 OTH AF: 0.226

Alfa AF: 0.178 Hom.: 489

Bravo AF: 0.273

Asia WGS AF: 0.414 AC: 1433 AN: 3464

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: rs28360317; hg19: chr5-82619558;