rs2074516

Positions:

• chr17-34998998-C-G

Variant summary

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

The NM_013975.4(LIG3):​c.2113+271C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 504,778 control chromosomes in the GnomAD database, including 14,438 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 0.26 (9351 hom., cov: 32)
  • Exomes 𝑓: 0.14 (5087 hom.)
• Consequence: LIG3 NM_013975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG3	NM_013975.4	c.2113+271C>G		intron_variant		ENST00000378526.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG3	ENST00000378526.9	c.2113+271C>G		intron_variant		1	NM_013975.4	P1
LIG3	ENST00000262327.9	c.2113+271C>G		intron_variant		1
LIG3	ENST00000593099.5	n.1658C>G		non_coding_transcript_exon_variant	2/6	2
LIG3	ENST00000586119.1	n.310+271C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39792 AN: 152016 Hom.: 9311 Cov.: 32

Gnomad AFR AF: 0.633

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.137 AC: 48243 AN: 352644 Hom.: 5087 Cov.: 4 AF XY: 0.135 AC XY: 24566 AN XY: 181850

Gnomad4 AFR exome AF: 0.633

Gnomad4 AMR exome AF: 0.118

Gnomad4 ASJ exome AF: 0.178

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.122

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.262 AC: 39880 AN: 152134 Hom.: 9351 Cov.: 32 AF XY: 0.259 AC XY: 19274 AN XY: 74374

Gnomad4 AFR AF: 0.633

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.222

Alfa AF: 0.203 Hom.: 751

Bravo AF: 0.275

Asia WGS AF: 0.238 AC: 829 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.59

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

Other links and lift over

dbSNP: rs2074516; hg19: chr17-33326017;