rs274883

chr19-48119288-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000234.3(LIG1):c.2386-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 942,708 control chromosomes in the GnomAD database, including 33,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (14280 hom., cov: 31)
  • Exomes 𝑓: 0.20 (19494 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.70

Genes affected

LIG1 (HGNC:6598): (DNA ligase 1) This gene encodes a member of the ATP-dependent DNA ligase protein family. The encoded protein functions in DNA replication, recombination, and the base excision repair process. Mutations in this gene that lead to DNA ligase I deficiency result in immunodeficiency and increased sensitivity to DNA-damaging agents. Disruption of this gene may also be associated with a variety of cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-48119288-A-G is Benign according to our data. Variant chr19-48119288-A-G is described in ClinVar as [Benign]. Clinvar id is 2628229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.2386-98T>C		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.2386-98T>C		intron_variant		1	NM_000234.3	P4
	ENST00000596563.5	n.69+788A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53075 AN: 151818 Hom.: 14240 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.196 AC: 154880 AN: 790772 Hom.: 19494 AF XY: 0.195 AC XY: 80386 AN XY: 412448

Gnomad4 AFR exome AF: 0.768

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.159

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.350 AC: 53164 AN: 151936 Hom.: 14280 Cov.: 31 AF XY: 0.344 AC XY: 25546 AN XY: 74246

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.180

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.296

Alfa AF: 0.200 Hom.: 6969

Bravo AF: 0.378

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

This variant is classified as Benign based on local population frequency. This variant was detected in 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.013
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: rs274883; hg19: chr19-48622545; COSMIC: COSV54392539; COSMIC: COSV54392539;