19-48119288-A-G

Variant names:

• chr19-48119288-A-G
• rs274883
• NM_000234.3:c.2386-98T>C

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]

ENSG00000269534 (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 rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2386-98T>C		intron_variant	Intron 24 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2386-98T>C		intron_variant	Intron 24 of 27	1	NM_000234.3	ENSP00000263274.6

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

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;