rs1193693

chr5-83241500-G-Achr5-83241500-G-T

Variant summary

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

The NM_003401.5(XRCC4):c.746-17030G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,576 control chromosomes in the GnomAD database, including 27,808 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 0.60 (27808 hom., cov: 31)
• Consequence: XRCC4 NM_003401.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XRCC4	NM_003401.5	c.746-17030G>A		intron_variant		ENST00000396027.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XRCC4	ENST00000396027.9	c.746-17030G>A		intron_variant		5	NM_003401.5	A1

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90096 AN: 151458 Hom.: 27752 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.595 AC: 90213 AN: 151576 Hom.: 27808 Cov.: 31 AF XY: 0.595 AC XY: 44010 AN XY: 73990

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.475

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.599

Alfa AF: 0.536 Hom.: 10058

Bravo AF: 0.612

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.82
Dann	Benign	0.14

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: rs1193693; hg19: chr5-82537319;