NM_000234.3:c.1821+486G>A

Variant names:

• chr19-48130590-C-T
• rs754948
• NM_000234.3:c.1821+486G>A

Variant summary

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

The NM_000234.3(LIG1):​c.1821+486G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,150 control chromosomes in the GnomAD database, including 1,841 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 0.12 (1841 hom., cov: 33)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 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.1821+486G>A		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.1818+486G>A		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.1731+486G>A		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.1821+486G>A		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.1818+486G>A		intron	N/A	ENSP00000471380.1
	LIG1	ENST00000916675.1		c.1923+486G>A		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18382 AN: 152032 Hom.: 1845 Cov.: 33

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.0697

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0447

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.121 AC: 18388 AN: 152150 Hom.: 1841 Cov.: 33 AF XY: 0.121 AC XY: 8966 AN XY: 74372

African (AFR) AF: 0.270 AC: 11199 AN: 41494

American (AMR) AF: 0.0896 AC: 1370 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0697 AC: 242 AN: 3470

East Asian (EAS) AF: 0.190 AC: 979 AN: 5166

South Asian (SAS) AF: 0.121 AC: 582 AN: 4818

European-Finnish (FIN) AF: 0.0649 AC: 688 AN: 10602

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0447 AC: 3041 AN: 67998

Other (OTH) AF: 0.111 AC: 235 AN: 2114

Alfa AF: 0.0657 Hom.: 847

Bravo AF: 0.128

Asia WGS AF: 0.150 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.16
DANN	Benign	0.49
PhyloP100		-2.5
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: rs754948; hg19: chr19-48633847;