rs3730840

Variant names:

• chr19-48170201-G-A
• rs3730840
• NM_000234.3:c.-58+40C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48170201-G-A
• chr19-48170201-G-C

Variant summary

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

The NM_000234.3(LIG1):​c.-58+40C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 454,550 control chromosomes in the GnomAD database, including 28,553 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 0.30 (8123 hom., cov: 31)
  • Exomes 𝑓: 0.36 (20430 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.-58+40C>T		intron_variant	Intron 1 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.-58+40C>T		intron_variant	Intron 1 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46058 AN: 151728 Hom.: 8120 Cov.: 31

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.322

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.287

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.330

GnomAD3 exomes AF: 0.356 AC: 45304 AN: 127110 Hom.: 8685 AF XY: 0.357 AC XY: 24875 AN XY: 69608

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.299

Gnomad ASJ exome AF: 0.332

Gnomad EAS exome AF: 0.577

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.356

GnomAD4 exome AF: 0.359 AC: 108642 AN: 302704 Hom.: 20430 Cov.: 0 AF XY: 0.357 AC XY: 61525 AN XY: 172482

Gnomad4 AFR exome AF: 0.126

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.328

Gnomad4 EAS exome AF: 0.575

Gnomad4 SAS exome AF: 0.308

Gnomad4 FIN exome AF: 0.417

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.303 AC: 46074 AN: 151846 Hom.: 8123 Cov.: 31 AF XY: 0.307 AC XY: 22765 AN XY: 74176

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.547

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.432

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.331

Alfa AF: 0.338 Hom.: 1736

Bravo AF: 0.289

Asia WGS AF: 0.435 AC: 1511 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.0
DANN	Benign	0.95

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: rs3730840; hg19: chr19-48673458;