chr13-108207930-TTAAG-T

Position:

• chr13-108207930-TTAAG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_206937.2(LIG4):​c.*599_*602del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,102 control chromosomes in the GnomAD database, including 1,588 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.13 (1588 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIG4 NM_206937.2 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.71

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 13-108207930-TTAAG-T is Benign according to our data. Variant chr13-108207930-TTAAG-T is described in ClinVar as [Likely_benign]. Clinvar id is 310957.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG4	NM_206937.2	c.*599_*602del		3_prime_UTR_variant	3/3	ENST00000442234.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG4	ENST00000442234.6	c.*599_*602del		3_prime_UTR_variant	3/3	1	NM_206937.2	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20338 AN: 151984 Hom.: 1587 Cov.: 30

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0604

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.158

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.134 AC: 20341 AN: 152102 Hom.: 1588 Cov.: 30 AF XY: 0.133 AC XY: 9863 AN XY: 74340

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0615

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.155

Alfa AF: 0.157 Hom.: 245

Bravo AF: 0.125

Asia WGS AF: 0.0310 AC: 105 AN: 3452

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

DNA ligase IV deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Severe combined immunodeficiency due to DCLRE1C deficiency Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3093770; hg19: chr13-108860278;