rs1805384

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_206937.2(LIG4):​c.-28-37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,142,904 control chromosomes in the GnomAD database, including 419 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 221 hom., cov: 32)
Exomes 𝑓: 0.0096 ( 198 hom. )

Consequence

LIG4
NM_206937.2 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.104
Variant links:
Genes affected
LIG4 (HGNC:6601): (DNA ligase 4) The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 13-108211333-A-G is Benign according to our data. Variant chr13-108211333-A-G is described in ClinVar as [Benign]. Clinvar id is 1247962.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
LIG4NM_206937.2 linkuse as main transcriptc.-28-37T>C intron_variant ENST00000442234.6 NP_996820.1 P49917A0A024RE06

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
LIG4ENST00000442234.6 linkuse as main transcriptc.-28-37T>C intron_variant 1 NM_206937.2 ENSP00000402030.1 P49917

Frequencies

GnomAD3 genomes
AF:
0.0349
AC:
5306
AN:
152150
Hom.:
221
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.102
Gnomad AMI
AF:
0.0285
Gnomad AMR
AF:
0.0257
Gnomad ASJ
AF:
0.0202
Gnomad EAS
AF:
0.00346
Gnomad SAS
AF:
0.0165
Gnomad FIN
AF:
0.00160
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.00622
Gnomad OTH
AF:
0.0296
GnomAD4 exome
AF:
0.00961
AC:
9519
AN:
990636
Hom.:
198
Cov.:
13
AF XY:
0.00955
AC XY:
4868
AN XY:
509788
show subpopulations
Gnomad4 AFR exome
AF:
0.104
Gnomad4 AMR exome
AF:
0.0134
Gnomad4 ASJ exome
AF:
0.0204
Gnomad4 EAS exome
AF:
0.00168
Gnomad4 SAS exome
AF:
0.0159
Gnomad4 FIN exome
AF:
0.00299
Gnomad4 NFE exome
AF:
0.00543
Gnomad4 OTH exome
AF:
0.0157
GnomAD4 genome
AF:
0.0349
AC:
5310
AN:
152268
Hom.:
221
Cov.:
32
AF XY:
0.0339
AC XY:
2523
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.101
Gnomad4 AMR
AF:
0.0256
Gnomad4 ASJ
AF:
0.0202
Gnomad4 EAS
AF:
0.00328
Gnomad4 SAS
AF:
0.0164
Gnomad4 FIN
AF:
0.00160
Gnomad4 NFE
AF:
0.00622
Gnomad4 OTH
AF:
0.0298
Alfa
AF:
0.0253
Hom.:
22
Bravo
AF:
0.0389
Asia WGS
AF:
0.0250
AC:
88
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxAug 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
6.5
DANN
Benign
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs1805384; hg19: chr13-108863681; API