rs274884

Positions:

• chr19-48118954-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000234.3(LIG1):​c.2439+183G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,040 control chromosomes in the GnomAD database, including 2,327 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 0.16 (2327 hom., cov: 31)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.82

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.275 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3	c.2439+183G>A		intron_variant		ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.2439+183G>A		intron_variant		1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24029 AN: 151922 Hom.: 2318 Cov.: 31

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0896

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0806

Gnomad FIN AF: 0.0870

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.158 AC: 24067 AN: 152040 Hom.: 2327 Cov.: 31 AF XY: 0.155 AC XY: 11542 AN XY: 74338

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0896

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0803

Gnomad4 FIN AF: 0.0870

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.129

Alfa AF: 0.144 Hom.: 238

Bravo AF: 0.168

Asia WGS AF: 0.124 AC: 429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.032
DANN	Benign	0.23

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: rs274884; hg19: chr19-48622211; COSMIC: COSV54393575; COSMIC: COSV54393575;