19-48161802-G-A

Position:

• chr19-48161802-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.108-295C>T		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.108-295C>T		intron_variant		1	NM_000234.3	P4

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

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.323

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.335

Alfa AF: 0.340 Hom.: 1209

Bravo AF: 0.295

Asia WGS AF: 0.441 AC: 1531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.36

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

Publications

LitVar

Other links and lift over

dbSNP: rs3730859; hg19: chr19-48665059;