dbSNP rs3730840: LIG1:c.-58+40C>T (chr19-48170201-G-A) – 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+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 454,550 control chromosomes in the GnomAD database, including 28,553 homozygotes. 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 0.30 ( 8123 hom., cov: 31)

Exomes 𝑓: 0.36 ( 20430 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

4 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

LIG1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000234.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.76).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 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	UniProt
LIG1	NM_000234.3	MANE Select	c.-58+40C>T	intron	N/A	NP_000225.1	P18858-1
LIG1	NM_001320970.2		c.-58+40C>T	intron	N/A	NP_001307899.1	A0A8V8TQC4
LIG1	NM_001320971.2		c.-58+40C>T	intron	N/A	NP_001307900.1	A0A8V8TPH8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LIG1	ENST00000263274.12	TSL:1 MANE Select	c.-58+40C>T	intron	N/A	ENSP00000263274.6	P18858-1
LIG1	ENST00000594759.5	TSL:1	n.-58+40C>T	intron	N/A	ENSP00000471380.1	M0R0Q7
LIG1	ENST00000699868.1		c.-200C>T	5_prime_UTR	Exon 1 of 28	ENSP00000514664.1	P18858-1

Frequencies

GnomAD3 genomes

AF:

0.304

AC:

46058

AN:

151728

Hom.:

8120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.322

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.547

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.287

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.330

GnomAD2 exomes

AF:

0.356

AC:

45304

AN:

127110

AF XY:

0.357

show subpopulations

Gnomad AFR exome

AF:

0.114

Gnomad AMR exome

AF:

0.299

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.577

Gnomad FIN exome

AF:

0.425

Gnomad NFE exome

AF:

0.383

Gnomad OTH exome

AF:

0.356

GnomAD4 exome

AF:

0.359

AC:

108642

AN:

302704

Hom.:

20430

Cov.:

AF XY:

0.357

AC XY:

61525

AN XY:

172482

show subpopulations

African (AFR)

AF:

0.126

AC:

1056

AN:

8380

American (AMR)

AF:

0.297

AC:

8087

AN:

27228

Ashkenazi Jewish (ASJ)

AF:

0.328

AC:

3522

AN:

10752

East Asian (EAS)

AF:

0.575

AC:

5222

AN:

9082

South Asian (SAS)

AF:

0.308

AC:

18401

AN:

59666

European-Finnish (FIN)

AF:

0.417

AC:

5147

AN:

12352

Middle Eastern (MID)

AF:

0.301

AC:

833

AN:

2772

European-Non Finnish (NFE)

AF:

0.386

AC:

61106

AN:

158302

Other (OTH)

AF:

0.372

AC:

5268

AN:

14170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4270

8539

12809

17078

21348

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

356

712

1068

1424

1780

<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:

0.303

AC:

46074

AN:

151846

Hom.:

8123

Cov.:

AF XY:

0.307

AC XY:

22765

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.121

AC:

5008

AN:

41486

American (AMR)

AF:

0.291

AC:

4437

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1096

AN:

3470

East Asian (EAS)

AF:

0.547

AC:

2770

AN:

5066

South Asian (SAS)

AF:

0.316

AC:

1525

AN:

4822

European-Finnish (FIN)

AF:

0.432

AC:

4547

AN:

10520

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.377

AC:

25615

AN:

67896

Other (OTH)

AF:

0.331

AC:

699

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1501

3002

4503

6004

7505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<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:

0.332

Hom.:

1743

Bravo

AF:

0.289

Asia WGS

AF:

0.435

AC:

1511

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

2.0

(source)

DANN

Benign

0.95

PhyloP100

-1.1

PromoterAI

0.018

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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