dbSNP rs3730842: LIG1:c.-58+498A>G (chr19-48169743-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+498A>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 0.20 ( 2250 hom., cov: 20)

Exomes 𝑓: 0.053 ( 0 hom. )

Consequence

LIG1
NM_000234.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.53

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

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 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+498A>G	intron	N/A	NP_000225.1	P18858-1
LIG1	NM_001320970.2		c.-58+498A>G	intron	N/A	NP_001307899.1	A0A8V8TQC4
LIG1	NM_001320971.2		c.-58+498A>G	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+498A>G	intron	N/A	ENSP00000263274.6	P18858-1
LIG1	ENST00000594759.5	TSL:1	n.-58+498A>G	intron	N/A	ENSP00000471380.1	M0R0Q7
LIG1	ENST00000916675.1		c.-58+498A>G	intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes

AF:

0.199

AC:

23335

AN:

117514

Hom.:

2251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.326

Gnomad AMI

AF:

0.0594

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.160

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.176

GnomAD4 exome

AF:

0.0533

AC:

AN:

394

Hom.:

Cov.:

AF XY:

0.0458

AC XY:

AN XY:

284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.167

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.0909

AC:

AN:

198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00658

AC:

AN:

152

Other (OTH)

AF:

0.0714

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.199

AC:

23354

AN:

117590

Hom.:

2250

Cov.:

AF XY:

0.198

AC XY:

11032

AN XY:

55806

show subpopulations

African (AFR)

AF:

0.326

AC:

10599

AN:

32480

American (AMR)

AF:

0.199

AC:

2111

AN:

10594

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

392

AN:

2870

East Asian (EAS)

AF:

0.159

AC:

569

AN:

3570

South Asian (SAS)

AF:

0.129

AC:

392

AN:

3036

European-Finnish (FIN)

AF:

0.135

AC:

809

AN:

5990

Middle Eastern (MID)

AF:

0.204

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.144

AC:

8114

AN:

56472

Other (OTH)

AF:

0.175

AC:

280

AN:

1598

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

857

1713

2570

3426

4283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

244

488

732

976

1220

<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:

0.145

Hom.:

300

Bravo

AF:

0.181

Asia WGS

AF:

0.114

AC:

397

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.1

(source)

DANN

Benign

0.21

PhyloP100

-1.5

PromoterAI

-0.12

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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