rs3730859

Variant names:

• chr19-48161802-G-A
• rs3730859
• NM_000234.3:c.108-295C>T

Variant summary

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

The NM_000234.3(LIG1):​c.108-295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 149,784 control chromosomes in the GnomAD database, including 8,095 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 0.31 (8095 hom., cov: 28)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 4 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.108-295C>T		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.108-295C>T		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.18-295C>T		intron	N/A	NP_001307900.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.108-295C>T		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.108-295C>T		intron	N/A	ENSP00000471380.1
	LIG1	ENST00000916675.1		c.108-295C>T		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 45921 AN: 149712 Hom.: 8090 Cov.: 28

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.307 AC: 45950 AN: 149784 Hom.: 8095 Cov.: 28 AF XY: 0.309 AC XY: 22493 AN XY: 72838

African (AFR) AF: 0.135 AC: 5508 AN: 40856

American (AMR) AF: 0.291 AC: 4378 AN: 15056

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1095 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2726 AN: 4938

South Asian (SAS) AF: 0.323 AC: 1540 AN: 4768

European-Finnish (FIN) AF: 0.424 AC: 4143 AN: 9770

Middle Eastern (MID) AF: 0.302 AC: 87 AN: 288

European-Non Finnish (NFE) AF: 0.377 AC: 25484 AN: 67650

Other (OTH) AF: 0.335 AC: 699 AN: 2088

Alfa AF: 0.331 Hom.: 1216

Bravo AF: 0.295

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.36
PhyloP100		0.14
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: rs3730859; hg19: chr19-48665059;