Genetic Variant LIG1:c.-58+286A>G (chr19-48169955-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000234.3(LIG1):c.-58+286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.51 ( 14245 hom., cov: 16)

Exomes 𝑓: 0.40 ( 4100 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

immunodeficiency 96
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

LIG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LIG1	NM_000234.3	MANE Select	c.-58+286A>G	intron	N/A	NP_000225.1
LIG1	NM_001320970.2		c.-58+286A>G	intron	N/A	NP_001307899.1
LIG1	NM_001320971.2		c.-58+286A>G	intron	N/A	NP_001307900.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LIG1	ENST00000263274.12	TSL:1 MANE Select	c.-58+286A>G	intron	N/A	ENSP00000263274.6
LIG1	ENST00000594759.5	TSL:1	n.-58+286A>G	intron	N/A	ENSP00000471380.1
LIG1	ENST00000699868.1		c.-58+104A>G	intron	N/A	ENSP00000514664.1

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

60439

AN:

117562

Hom.:

14213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.485

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.406

Gnomad EAS

AF:

0.766

Gnomad SAS

AF:

0.499

Gnomad FIN

AF:

0.583

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.516

GnomAD4 exome

AF:

0.403

AC:

21918

AN:

54358

Hom.:

4100

Cov.:

AF XY:

0.409

AC XY:

13291

AN XY:

32468

show subpopulations

African (AFR)

AF:

0.576

AC:

160

AN:

278

American (AMR)

AF:

0.320

AC:

123

AN:

384

Ashkenazi Jewish (ASJ)

AF:

0.339

AC:

371

AN:

1096

East Asian (EAS)

AF:

0.810

AC:

AN:

116

South Asian (SAS)

AF:

0.414

AC:

7405

AN:

17890

European-Finnish (FIN)

AF:

0.458

AC:

1402

AN:

3062

Middle Eastern (MID)

AF:

0.333

AC:

AN:

162

European-Non Finnish (NFE)

AF:

0.390

AC:

11346

AN:

29074

Other (OTH)

AF:

0.419

AC:

963

AN:

2296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

657

1314

1971

2628

3285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.514

AC:

60525

AN:

117676

Hom.:

14245

Cov.:

AF XY:

0.524

AC XY:

29040

AN XY:

55472

show subpopulations

African (AFR)

AF:

0.604

AC:

19461

AN:

32246

American (AMR)

AF:

0.504

AC:

5082

AN:

10092

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1160

AN:

2858

East Asian (EAS)

AF:

0.766

AC:

3259

AN:

4252

South Asian (SAS)

AF:

0.499

AC:

1709

AN:

3424

European-Finnish (FIN)

AF:

0.583

AC:

3551

AN:

6092

Middle Eastern (MID)

AF:

0.517

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.445

AC:

25023

AN:

56192

Other (OTH)

AF:

0.517

AC:

829

AN:

1602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

1428

2857

4285

5714

7142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

546

1092

1638

2184

2730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.435

Hom.:

1883

Bravo

AF:

0.460

Asia WGS

AF:

0.597

AC:

2071

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.5

(source)

DANN

Benign

0.53

PhyloP100

-1.9

PromoterAI

0.029

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over