rs3730931

chr19-48143984-T-Cchr19-48143984-T-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/exons	MANE	UniProt
LIG1	NM_000234.3	c.777-21A>G		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.777-21A>G		intron_variant		1	NM_000234.3	P4

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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Nov 12, 2023

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;