rs3730872

chr19-48156434-G-Achr19-48156434-G-T

Variant summary

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

The NM_000234.3(LIG1):c.370+580C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,154 control chromosomes in the GnomAD database, including 2,239 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 0.15 (2239 hom., cov: 33)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624

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 (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.370+580C>T		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.370+580C>T		intron_variant		1	NM_000234.3	P4

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23239 AN: 152036 Hom.: 2237 Cov.: 33

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0787

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.153 AC: 23260 AN: 152154 Hom.: 2239 Cov.: 33 AF XY: 0.150 AC XY: 11123 AN XY: 74386

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0795

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0814

Gnomad4 FIN AF: 0.0787

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.130

Alfa AF: 0.105 Hom.: 1964

Bravo AF: 0.164

Asia WGS AF: 0.119 AC: 414 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	2.4
Dann	Benign	0.68

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: rs3730872; hg19: chr19-48659691; COSMIC: COSV54395689; COSMIC: COSV54395689;