rs4796030

Positions:

• chr17-35003131-A-C

Variant summary

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

The NM_002311.5(LIG3):​c.*83A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 1,588,152 control chromosomes in the GnomAD database, including 265,488 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 0.65 (33590 hom., cov: 30)
  • Exomes 𝑓: 0.56 (231898 hom.)
• Consequence: LIG3 NM_002311.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

Genes affected

LIG3 (HGNC:6600): (DNA ligase 3) This gene is a member of the DNA ligase family. Each member of this family encodes a protein that catalyzes the joining of DNA ends but they each have a distinct role in DNA metabolism. The protein encoded by this gene is involved in excision repair and is located in both the mitochondria and nucleus, with translation initiation from the upstream start codon allowing for transport to the mitochondria and translation initiation from a downstream start codon allowing for transport to the nucleus. Additionally, alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

LIG3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.2796+342A>C		intron_variant		ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000262327.9	c.*83A>C		3_prime_UTR_variant	20/20	1		ENSP00000262327.4
LIG3	ENST00000378526.9	c.2796+342A>C		intron_variant		1	NM_013975.4	ENSP00000367787.3
LIG3	ENST00000592244.1	n.298A>C		non_coding_transcript_exon_variant	1/2	3
LIG3	ENST00000593099.5	n.2991A>C		non_coding_transcript_exon_variant	6/6	2

Frequencies

GnomAD3 genomes AF: 0.651 AC: 98771 AN: 151836 Hom.: 33543 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.551

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.561

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.565 AC: 811159 AN: 1436198 Hom.: 231898 Cov.: 39 AF XY: 0.565 AC XY: 402042 AN XY: 712172

Gnomad4 AFR exome AF: 0.866

Gnomad4 AMR exome AF: 0.542

Gnomad4 ASJ exome AF: 0.532

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.576

Gnomad4 FIN exome AF: 0.694

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.575

GnomAD4 genome AF: 0.651 AC: 98870 AN: 151954 Hom.: 33590 Cov.: 30 AF XY: 0.653 AC XY: 48518 AN XY: 74252

Gnomad4 AFR AF: 0.855

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.618

Alfa AF: 0.566 Hom.: 35024

Bravo AF: 0.644

Asia WGS AF: 0.600 AC: 2088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.56

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: rs4796030; hg19: chr17-33330150;