19-48128151-C-T

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.1822-131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 740,756 control chromosomes in the GnomAD database, including 49,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (7915 hom., cov: 31)
  • Exomes 𝑓: 0.37 (41176 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.349

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-48128151-C-T is Benign according to our data. Variant chr19-48128151-C-T is described in ClinVar as [Benign]. Clinvar id is 2628277.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.1822-131G>A		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.1822-131G>A		intron_variant		1	NM_000234.3	P4

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45476 AN: 151858 Hom.: 7910 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.306

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.366 AC: 215208 AN: 588780 Hom.: 41176 AF XY: 0.365 AC XY: 116214 AN XY: 318462

Gnomad4 AFR exome AF: 0.122

Gnomad4 AMR exome AF: 0.292

Gnomad4 ASJ exome AF: 0.317

Gnomad4 EAS exome AF: 0.565

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.373

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.299 AC: 45497 AN: 151976 Hom.: 7915 Cov.: 31 AF XY: 0.302 AC XY: 22462 AN XY: 74302

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.306

Gnomad4 EAS AF: 0.554

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.325

Alfa AF: 0.344 Hom.: 5062

Bravo AF: 0.284

Asia WGS AF: 0.444 AC: 1542 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 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.80
Dann	Benign	0.64

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: rs156641; hg19: chr19-48631408; COSMIC: COSV54390776; COSMIC: COSV54390776;