rs3730865

Positions:

• chr19-48157254-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000234.3(LIG1):​c.244-114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0375 in 1,233,244 control chromosomes in the GnomAD database, including 1,036 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 0.026 (76 hom., cov: 31)
  • Exomes 𝑓: 0.039 (960 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0255 (3886/152184) while in subpopulation NFE AF= 0.0416 (2827/68002). AF 95% confidence interval is 0.0403. There are 76 homozygotes in gnomad4. There are 1779 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 76 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3	c.244-114T>C		intron_variant		ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.244-114T>C		intron_variant		1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3889 AN: 152066 Hom.: 76 Cov.: 31

Gnomad AFR AF: 0.00804

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0262

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0214

Gnomad FIN AF: 0.00529

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0368

GnomAD4 exome AF: 0.0392 AC: 42371 AN: 1081060 Hom.: 960 AF XY: 0.0388 AC XY: 20782 AN XY: 535190

Gnomad4 AFR exome AF: 0.00598

Gnomad4 AMR exome AF: 0.0209

Gnomad4 ASJ exome AF: 0.0183

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.00669

Gnomad4 NFE exome AF: 0.0457

Gnomad4 OTH exome AF: 0.0348

GnomAD4 genome AF: 0.0255 AC: 3886 AN: 152184 Hom.: 76 Cov.: 31 AF XY: 0.0239 AC XY: 1779 AN XY: 74396

Gnomad4 AFR AF: 0.00802

Gnomad4 AMR AF: 0.0262

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0212

Gnomad4 FIN AF: 0.00529

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0292 Hom.: 10

Bravo AF: 0.0270

Asia WGS AF: 0.00606 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.97
DANN	Benign	0.79

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: rs3730865; hg19: chr19-48660511;