chr19-48121955-G-A

Variant names:

• chr19-48121955-G-A
• rs156645
• NM_000234.3:c.2233-633C>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.2233-633C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,112 control chromosomes in the GnomAD database, including 7,759 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 0.29 (7759 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• 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)

ENSG00000269534 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2233-633C>T		intron_variant	Intron 23 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2233-633C>T		intron_variant	Intron 23 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44039 AN: 151994 Hom.: 7753 Cov.: 32

Gnomad AFR AF: 0.0879

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.302

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.370

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.290 AC: 44055 AN: 152112 Hom.: 7759 Cov.: 32 AF XY: 0.293 AC XY: 21773 AN XY: 74356

African (AFR) AF: 0.0877 AC: 3641 AN: 41530

American (AMR) AF: 0.274 AC: 4190 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.302 AC: 1050 AN: 3472

East Asian (EAS) AF: 0.554 AC: 2859 AN: 5160

South Asian (SAS) AF: 0.324 AC: 1563 AN: 4818

European-Finnish (FIN) AF: 0.430 AC: 4548 AN: 10572

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.370 AC: 25164 AN: 67978

Other (OTH) AF: 0.319 AC: 674 AN: 2110

Alfa AF: 0.335 Hom.: 3241

Bravo AF: 0.272

Asia WGS AF: 0.439 AC: 1527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.77
DANN	Benign	0.53
PhyloP100		-0.57
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: rs156645; hg19: chr19-48625212;