rs2074518

Positions:

• chr17-34997363-C-T

Variant summary

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

The ENST00000378526.9(LIG3):​c.1824-375C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 189,094 control chromosomes in the GnomAD database, including 15,177 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 0.37 (11930 hom., cov: 32)
  • Exomes 𝑓: 0.40 (3247 hom.)
• Consequence: LIG3 ENST00000378526.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.395

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG3	NM_013975.4	c.1824-375C>T		intron_variant		ENST00000378526.9	NP_039269.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG3	ENST00000378526.9	c.1824-375C>T		intron_variant		1	NM_013975.4	ENSP00000367787	P1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56397 AN: 151844 Hom.: 11933 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.400

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 0.397 AC: 14749 AN: 37132 Hom.: 3247 Cov.: 0 AF XY: 0.396 AC XY: 7888 AN XY: 19938

Gnomad4 AFR exome AF: 0.142

Gnomad4 AMR exome AF: 0.407

Gnomad4 ASJ exome AF: 0.357

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.555

Gnomad4 NFE exome AF: 0.449

Gnomad4 OTH exome AF: 0.401

GnomAD4 genome AF: 0.371 AC: 56394 AN: 151962 Hom.: 11930 Cov.: 32 AF XY: 0.376 AC XY: 27950 AN XY: 74260

Gnomad4 AFR AF: 0.166

Gnomad4 AMR AF: 0.400

Gnomad4 ASJ AF: 0.340

Gnomad4 EAS AF: 0.287

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.570

Gnomad4 NFE AF: 0.465

Gnomad4 OTH AF: 0.380

Alfa AF: 0.436 Hom.: 17658

Bravo AF: 0.350

Asia WGS AF: 0.350 AC: 1211 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.71
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: rs2074518; hg19: chr17-33324382;