13-108215053-A-G

Position:

• chr13-108215053-A-G

Variant summary

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

The ENST00000442234.6(LIG4):​c.-102+431T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.092 (311 hom., cov: 9)
• Consequence: LIG4 ENST00000442234.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG4	NM_206937.2	c.-102+431T>C		intron_variant		ENST00000442234.6	NP_996820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG4	ENST00000442234.6	c.-102+431T>C		intron_variant		1	NM_206937.2	ENSP00000402030	P1

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 4990 AN: 54290 Hom.: 311 Cov.: 9

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0837

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0909

Gnomad OTH AF: 0.0899

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

GnomAD4 genome AF: 0.0918 AC: 4990 AN: 54330 Hom.: 311 Cov.: 9 AF XY: 0.0916 AC XY: 2293 AN XY: 25024

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0831

Gnomad4 FIN AF: 0.0988

Gnomad4 NFE AF: 0.0909

Gnomad4 OTH AF: 0.0908

Alfa AF: 0.114 Hom.: 139

Bravo AF: 0.130

Asia WGS AF: 0.103 AC: 332 AN: 3234

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.19
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3093739; hg19: chr13-108867401;