rs10080123

chr5-83165447-A-Cchr5-83165447-A-G

Variant summary

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

The NM_003401.5(XRCC4):c.316-30323A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 151,932 control chromosomes in the GnomAD database, including 12,966 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 0.40 (12966 hom., cov: 32)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.343

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC4	NM_003401.5	c.316-30323A>C		intron_variant		ENST00000396027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC4	ENST00000396027.9	c.316-30323A>C		intron_variant		5	NM_003401.5	A1

Frequencies

GnomAD3 genomes AF: 0.405 AC: 61479 AN: 151814 Hom.: 12959 Cov.: 32

Gnomad AFR AF: 0.411

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0616

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.405 AC: 61507 AN: 151932 Hom.: 12966 Cov.: 32 AF XY: 0.405 AC XY: 30052 AN XY: 74254

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.0614

Gnomad4 SAS AF: 0.485

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.398

Alfa AF: 0.399 Hom.: 5683

Bravo AF: 0.387

Asia WGS AF: 0.287 AC: 996 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.4
Dann	Benign	0.66

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: rs10080123; hg19: chr5-82461266;