19-48143984-T-C

Variant names:

• chr19-48143984-T-C
• rs3730931
• NM_000234.3:c.777-21A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000234.3(LIG1):​c.777-21A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,579,302 control chromosomes in the GnomAD database, including 12,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (2023 hom., cov: 31)
  • Exomes 𝑓: 0.12 (10302 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.25

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 19-48143984-T-C is Benign according to our data. Variant chr19-48143984-T-C is described in ClinVar as [Benign]. Clinvar id is 2628268.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.777-21A>G		intron_variant	Intron 9 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.777-21A>G		intron_variant	Intron 9 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22965 AN: 151866 Hom.: 2022 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0899

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0815

Gnomad FIN AF: 0.0862

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.119 AC: 29971 AN: 251408 Hom.: 2055 AF XY: 0.114 AC XY: 15467 AN XY: 135890

Gnomad AFR exome AF: 0.267

Gnomad AMR exome AF: 0.134

Gnomad ASJ exome AF: 0.0835

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.0831

Gnomad FIN exome AF: 0.0887

Gnomad NFE exome AF: 0.112

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.117 AC: 166592 AN: 1427318 Hom.: 10302 Cov.: 28 AF XY: 0.115 AC XY: 81885 AN XY: 712344

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.0855

Gnomad4 EAS exome AF: 0.0991

Gnomad4 SAS exome AF: 0.0824

Gnomad4 FIN exome AF: 0.0908

Gnomad4 NFE exome AF: 0.117

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.151 AC: 22984 AN: 151984 Hom.: 2023 Cov.: 31 AF XY: 0.148 AC XY: 10979 AN XY: 74290

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0899

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.0812

Gnomad4 FIN AF: 0.0862

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.127

Alfa AF: 0.137 Hom.: 553

Bravo AF: 0.160

Asia WGS AF: 0.120 AC: 419 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 24% of patients studied by a panel of primary immunodeficiencies. Number of patients: 23. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs3730931; hg19: chr19-48647241; COSMIC: COSV54391159; COSMIC: COSV54391159;