19-48153314-T-G

Variant names:

• chr19-48153314-T-G
• rs3730895
• NM_000234.3:c.466+558A>C

Variant summary

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

The NM_000234.3(LIG1):​c.466+558A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,290 control chromosomes in the GnomAD database, including 16,457 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 0.46 (16457 hom., cov: 29)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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)

LIG1-AS1 (HGNC:58602):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.466+558A>C		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.466+558A>C		intron_variant	Intron 6 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70056 AN: 151174 Hom.: 16443 Cov.: 29

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.463 AC: 70107 AN: 151290 Hom.: 16457 Cov.: 29 AF XY: 0.463 AC XY: 34191 AN XY: 73838

African (AFR) AF: 0.436 AC: 17977 AN: 41198

American (AMR) AF: 0.422 AC: 6397 AN: 15160

Ashkenazi Jewish (ASJ) AF: 0.399 AC: 1381 AN: 3464

East Asian (EAS) AF: 0.675 AC: 3482 AN: 5156

South Asian (SAS) AF: 0.404 AC: 1932 AN: 4786

European-Finnish (FIN) AF: 0.513 AC: 5314 AN: 10356

Middle Eastern (MID) AF: 0.397 AC: 116 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32195 AN: 67868

Other (OTH) AF: 0.461 AC: 969 AN: 2100

Alfa AF: 0.404 Hom.: 2211

Bravo AF: 0.460

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.60
PhyloP100		-1.0
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: rs3730895; hg19: chr19-48656571;