5-83126824-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003401.5(XRCC4):​c.315+15621G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,046 control chromosomes in the GnomAD database, including 17,303 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 0.46 ( 17303 hom., cov: 33)

Consequence

XRCC4
NM_003401.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.241
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
XRCC4NM_003401.5 linkuse as main transcriptc.315+15621G>A intron_variant ENST00000396027.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
XRCC4ENST00000396027.9 linkuse as main transcriptc.315+15621G>A intron_variant 5 NM_003401.5 A1Q13426-2

Frequencies

GnomAD3 genomes
AF:
0.465
AC:
70576
AN:
151928
Hom.:
17286
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.589
Gnomad AMI
AF:
0.522
Gnomad AMR
AF:
0.326
Gnomad ASJ
AF:
0.370
Gnomad EAS
AF:
0.138
Gnomad SAS
AF:
0.492
Gnomad FIN
AF:
0.449
Gnomad MID
AF:
0.389
Gnomad NFE
AF:
0.450
Gnomad OTH
AF:
0.437
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.464
AC:
70623
AN:
152046
Hom.:
17303
Cov.:
33
AF XY:
0.462
AC XY:
34334
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.589
Gnomad4 AMR
AF:
0.325
Gnomad4 ASJ
AF:
0.370
Gnomad4 EAS
AF:
0.137
Gnomad4 SAS
AF:
0.491
Gnomad4 FIN
AF:
0.449
Gnomad4 NFE
AF:
0.450
Gnomad4 OTH
AF:
0.438
Alfa
AF:
0.450
Hom.:
14739
Bravo
AF:
0.453
Asia WGS
AF:
0.328
AC:
1141
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
5.3
DANN
Benign
0.63

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1120476; hg19: chr5-82422643; API