19-48153314-T-G

Variant names:

• chr19-48153314-T-G
• rs3730895
• NM_000234.3:c.466+558A>C

Variant summary

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

The NM_000234.3(LIG1):​c.466+558A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 151,290 control chromosomes in the GnomAD database, including 16,457 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 0.46 (16457 hom., cov: 29)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.466+558A>C		intron_variant	Intron 6 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.466+558A>C		intron_variant	Intron 6 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70056 AN: 151174 Hom.: 16443 Cov.: 29

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.463 AC: 70107 AN: 151290 Hom.: 16457 Cov.: 29 AF XY: 0.463 AC XY: 34191 AN XY: 73838

Gnomad4 AFR AF: 0.436

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.675

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.461

Alfa AF: 0.403 Hom.: 2143

Bravo AF: 0.460

Asia WGS AF: 0.563 AC: 1956 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.60

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: rs3730895; hg19: chr19-48656571;