chr19-48117779-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000234.3(LIG1):c.2442G>C(p.Ala814Ala) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,611,088 control chromosomes in the GnomAD database, including 162,858 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. A814A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.47 ( 17579 hom., cov: 34)

Exomes 𝑓: 0.44 ( 145279 hom. )

Consequence

LIG1
NM_000234.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.688

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 19-48117779-C-G is Benign according to our data. Variant chr19-48117779-C-G is described in ClinVar as [Benign]. Clinvar id is 403033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.688 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.73 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3 link	c.2442G>C	p.Ala814Ala	splice_region_variant, synonymous_variant	Exon 26 of 28	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.2442G>C	p.Ala814Ala	splice_region_variant, synonymous_variant	Exon 26 of 28	1	NM_000234.3	ENSP00000263274.6		P18858-1

Frequencies

GnomAD3 genomes

AF:

0.475

AC:

72135

AN:

152012

Hom.:

17560

Cov.:

show subpopulations

Gnomad AFR

AF:

0.544

Gnomad AMI

AF:

0.461

Gnomad AMR

AF:

0.402

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.750

Gnomad SAS

AF:

0.473

Gnomad FIN

AF:

0.497

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.479

GnomAD2 exomes

AF:

0.463

AC:

113343

AN:

244628

AF XY:

0.464

show subpopulations

Gnomad AFR exome

AF:

0.541

Gnomad AMR exome

AF:

0.374

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.754

Gnomad FIN exome

AF:

0.492

Gnomad NFE exome

AF:

0.429

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.441

AC:

643367

AN:

1458958

Hom.:

145279

Cov.:

AF XY:

0.442

AC XY:

320384

AN XY:

725416

show subpopulations

African (AFR)

AF:

0.547

AC:

18295

AN:

33458

American (AMR)

AF:

0.381

AC:

16865

AN:

44310

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

10351

AN:

25994

East Asian (EAS)

AF:

0.769

AC:

30484

AN:

39634

South Asian (SAS)

AF:

0.468

AC:

40030

AN:

85560

European-Finnish (FIN)

AF:

0.483

AC:

25648

AN:

53140

Middle Eastern (MID)

AF:

0.464

AC:

2678

AN:

5766

European-Non Finnish (NFE)

AF:

0.424

AC:

471218

AN:

1110802

Other (OTH)

AF:

0.461

AC:

27798

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

19615

39229

58844

78458

98073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.475

AC:

72196

AN:

152130

Hom.:

17579

Cov.:

AF XY:

0.475

AC XY:

35353

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.544

AC:

22573

AN:

41496

American (AMR)

AF:

0.402

AC:

6140

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.393

AC:

1363

AN:

3470

East Asian (EAS)

AF:

0.750

AC:

3879

AN:

5174

South Asian (SAS)

AF:

0.474

AC:

2285

AN:

4822

European-Finnish (FIN)

AF:

0.497

AC:

5273

AN:

10602

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29105

AN:

67974

Other (OTH)

AF:

0.481

AC:

1015

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2002

4004

6006

8008

10010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.400

Hom.:

3715

Bravo

AF:

0.474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

8.5

(source)

DANN

Benign

0.78

PhyloP100

0.69

Mutation Taster

=94/6

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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chr19-48117779-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over