chr19-48127506-G-C

Variant names:

• chr19-48127506-G-C
• rs156640
• NM_000234.3:c.1933-158C>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.1933-158C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 687,764 control chromosomes in the GnomAD database, including 78,854 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 0.48 (17786 hom., cov: 33)
  • Exomes 𝑓: 0.47 (61068 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.01
• 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)

ENSG00000269534 (HGNC:):

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 = 0.729 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.1933-158C>G		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.1930-158C>G		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.1843-158C>G		intron	N/A	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.1933-158C>G		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.1930-158C>G		intron	N/A	ENSP00000471380.1
	ENSG00000269534	ENST00000596563.5	TSL:2	n.652G>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.477 AC: 72499 AN: 151920 Hom.: 17763 Cov.: 33

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.459

Gnomad AMR AF: 0.402

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.469 AC: 251006 AN: 535726 Hom.: 61068 Cov.: 6 AF XY: 0.469 AC XY: 133823 AN XY: 285236

African (AFR) AF: 0.558 AC: 9064 AN: 16256

American (AMR) AF: 0.405 AC: 12460 AN: 30776

Ashkenazi Jewish (ASJ) AF: 0.405 AC: 6630 AN: 16364

East Asian (EAS) AF: 0.774 AC: 26647 AN: 34432

South Asian (SAS) AF: 0.477 AC: 27274 AN: 57194

European-Finnish (FIN) AF: 0.486 AC: 16043 AN: 33034

Middle Eastern (MID) AF: 0.472 AC: 1107 AN: 2344

European-Non Finnish (NFE) AF: 0.436 AC: 137711 AN: 315864

Other (OTH) AF: 0.478 AC: 14070 AN: 29462

GnomAD4 genome AF: 0.477 AC: 72566 AN: 152038 Hom.: 17786 Cov.: 33 AF XY: 0.478 AC XY: 35503 AN XY: 74296

African (AFR) AF: 0.554 AC: 22974 AN: 41462

American (AMR) AF: 0.402 AC: 6151 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1367 AN: 3466

East Asian (EAS) AF: 0.749 AC: 3869 AN: 5168

South Asian (SAS) AF: 0.476 AC: 2292 AN: 4820

European-Finnish (FIN) AF: 0.496 AC: 5246 AN: 10566

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29095 AN: 67966

Other (OTH) AF: 0.480 AC: 1008 AN: 2100

Alfa AF: 0.321 Hom.: 810

Bravo AF: 0.477

Asia WGS AF: 0.617 AC: 2148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.018
DANN	Benign	0.50
PhyloP100		-3.0
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: rs156640; hg19: chr19-48630763;