rs3730913

chr19-48149543-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.776+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,024 control chromosomes in the GnomAD database, including 8,158 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 (8158 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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]

LOC107985293 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.776+220C>T		intron_variant		ENST00000263274.12
LOC107985293	XR_007067281.1	n.177+3425G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.776+220C>T		intron_variant		1	NM_000234.3	P4

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43363 AN: 151906 Hom.: 8160 Cov.: 32

Gnomad AFR AF: 0.543

Gnomad AMI AF: 0.217

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.254

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

GnomAD4 genome AF: 0.285 AC: 43391 AN: 152024 Hom.: 8158 Cov.: 32 AF XY: 0.282 AC XY: 20928 AN XY: 74330

Gnomad4 AFR AF: 0.543

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.254

Alfa AF: 0.188 Hom.: 6177

Bravo AF: 0.304

Asia WGS AF: 0.277 AC: 965 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.086
Dann	Benign	0.44

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: rs3730913; hg19: chr19-48652800; COSMIC: COSV54395492; COSMIC: COSV54395492;