19-48151296-G-T

Variant names:

• chr19-48151296-G-T
• rs20580
• NM_000234.3:c.510C>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000234.3(LIG1):​c.510C>A​(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,610,878 control chromosomes in the GnomAD database, including 195,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19396 hom., cov: 29)
  • Exomes 𝑓: 0.49 (175772 hom.)
• Consequence: LIG1 NM_000234.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.130
• Publications: 39 publications found

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-AS1 (HGNC:58602):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 19-48151296-G-T is Benign according to our data. Variant chr19-48151296-G-T is described in ClinVar as Benign. ClinVar VariationId is 403037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.13 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.655 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.510C>A	p.Ala170Ala	synonymous	Exon 7 of 28	NP_000225.1
	LIG1	NM_001320970.2		c.507C>A	p.Ala169Ala	synonymous	Exon 7 of 28	NP_001307899.1
	LIG1	NM_001320971.2		c.420C>A	p.Ala140Ala	synonymous	Exon 6 of 27	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.510C>A	p.Ala170Ala	synonymous	Exon 7 of 28	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.507C>A		non_coding_transcript_exon	Exon 7 of 28	ENSP00000471380.1
	LIG1	ENST00000699868.1		c.510C>A	p.Ala170Ala	synonymous	Exon 7 of 28	ENSP00000514664.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76155 AN: 151572 Hom.: 19373 Cov.: 29

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.491

GnomAD2 exomes AF: 0.488 AC: 122770 AN: 251442 AF XY: 0.483

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.436

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.706

Gnomad FIN exome AF: 0.512

Gnomad NFE exome AF: 0.486

Gnomad OTH exome AF: 0.467

GnomAD4 exome AF: 0.488 AC: 712022 AN: 1459190 Hom.: 175772 Cov.: 36 AF XY: 0.485 AC XY: 352052 AN XY: 726052

African (AFR) AF: 0.541 AC: 18064 AN: 33410

American (AMR) AF: 0.437 AC: 19561 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 10809 AN: 26108

East Asian (EAS) AF: 0.664 AC: 26337 AN: 39678

South Asian (SAS) AF: 0.397 AC: 34227 AN: 86204

European-Finnish (FIN) AF: 0.506 AC: 27004 AN: 53400

Middle Eastern (MID) AF: 0.392 AC: 2263 AN: 5766

European-Non Finnish (NFE) AF: 0.490 AC: 543973 AN: 1109620

Other (OTH) AF: 0.494 AC: 29784 AN: 60292

GnomAD4 genome AF: 0.503 AC: 76229 AN: 151688 Hom.: 19396 Cov.: 29 AF XY: 0.500 AC XY: 37051 AN XY: 74102

African (AFR) AF: 0.546 AC: 22594 AN: 41378

American (AMR) AF: 0.443 AC: 6752 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1428 AN: 3462

East Asian (EAS) AF: 0.674 AC: 3461 AN: 5138

South Asian (SAS) AF: 0.404 AC: 1933 AN: 4790

European-Finnish (FIN) AF: 0.518 AC: 5442 AN: 10514

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.488 AC: 33128 AN: 67876

Other (OTH) AF: 0.491 AC: 1030 AN: 2096

Alfa AF: 0.491 Hom.: 55252

Bravo AF: 0.505

Asia WGS AF: 0.574 AC: 1994 AN: 3478

EpiCase AF: 0.481

EpiControl AF: 0.476

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

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 72% of patients studied by a panel of primary immunodeficiencies. Number of patients: 69. 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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.48
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs20580; hg19: chr19-48654553; COSMIC: COSV54392266; COSMIC: COSV54392266;