Genetic Variant LIG1:c.1822-131G>A (chr19-48128151-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.349

Variant links:

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]

LIG1 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.1822-131G>A		intron_variant	Intron 19 of 27	ENST00000263274.12	NP_000225.1	P18858-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12 link	c.1822-131G>A		intron_variant	Intron 19 of 27	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45476

AN:

151858

Hom.:

7910

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.302

AC XY:

22462

AN XY:

74302

show subpopulations

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

LINK: link

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 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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over