rs8100261

Variant names:

• chr19-48152502-T-C
• rs8100261
• NM_000234.3:c.467-1163A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000234.3(LIG1):​c.467-1163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,052 control chromosomes in the GnomAD database, including 32,454 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 0.64 (32454 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.644
• Publications: 10 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.467-1163A>G		intron_variant	Intron 6 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.467-1163A>G		intron_variant	Intron 6 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96483 AN: 151934 Hom.: 32402 Cov.: 32

Gnomad AFR AF: 0.859

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.481

Gnomad EAS AF: 0.868

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.610

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.635 AC: 96592 AN: 152052 Hom.: 32454 Cov.: 32 AF XY: 0.633 AC XY: 47050 AN XY: 74302

African (AFR) AF: 0.860 AC: 35698 AN: 41532

American (AMR) AF: 0.540 AC: 8239 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.481 AC: 1665 AN: 3464

East Asian (EAS) AF: 0.868 AC: 4487 AN: 5168

South Asian (SAS) AF: 0.533 AC: 2567 AN: 4812

European-Finnish (FIN) AF: 0.577 AC: 6098 AN: 10566

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.529 AC: 35907 AN: 67936

Other (OTH) AF: 0.611 AC: 1290 AN: 2112

Alfa AF: 0.569 Hom.: 66864

Bravo AF: 0.648

Asia WGS AF: 0.735 AC: 2557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.42
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8100261; hg19: chr19-48655759;