rs274883

Variant names:

• chr19-48119288-A-G
• rs274883
• NM_000234.3:c.2386-98T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-48119288-A-G
• chr19-48119288-A-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000234.3(LIG1):​c.2386-98T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 942,708 control chromosomes in the GnomAD database, including 33,774 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (14280 hom., cov: 31)
  • Exomes 𝑓: 0.20 (19494 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.70
• Publications: 29 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 96

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ENSG00000269534 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 19-48119288-A-G is Benign according to our data. Variant chr19-48119288-A-G is described in ClinVar as Benign. ClinVar VariationId is 2628229.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.2386-98T>C		intron	N/A	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.2383-98T>C		intron	N/A	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.2296-98T>C		intron	N/A	NP_001307900.1	A0A8V8TPH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.2386-98T>C		intron	N/A	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.*983-98T>C		intron	N/A	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000916675.1		c.2488-98T>C		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53075 AN: 151818 Hom.: 14240 Cov.: 31

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.296

GnomAD4 exome AF: 0.196 AC: 154880 AN: 790772 Hom.: 19494 AF XY: 0.195 AC XY: 80386 AN XY: 412448

African (AFR) AF: 0.768 AC: 15039 AN: 19590

American (AMR) AF: 0.235 AC: 8212 AN: 34934

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 3616 AN: 21414

East Asian (EAS) AF: 0.302 AC: 9901 AN: 32814

South Asian (SAS) AF: 0.228 AC: 15292 AN: 67088

European-Finnish (FIN) AF: 0.159 AC: 7393 AN: 46542

Middle Eastern (MID) AF: 0.243 AC: 1101 AN: 4530

European-Non Finnish (NFE) AF: 0.163 AC: 85485 AN: 525778

Other (OTH) AF: 0.232 AC: 8841 AN: 38082

GnomAD4 genome AF: 0.350 AC: 53164 AN: 151936 Hom.: 14280 Cov.: 31 AF XY: 0.344 AC XY: 25546 AN XY: 74246

African (AFR) AF: 0.759 AC: 31449 AN: 41436

American (AMR) AF: 0.268 AC: 4091 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 624 AN: 3466

East Asian (EAS) AF: 0.314 AC: 1620 AN: 5156

South Asian (SAS) AF: 0.228 AC: 1099 AN: 4828

European-Finnish (FIN) AF: 0.153 AC: 1620 AN: 10558

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11755 AN: 67924

Other (OTH) AF: 0.296 AC: 625 AN: 2112

Alfa AF: 0.236 Hom.: 17159

Bravo AF: 0.378

Asia WGS AF: 0.303 AC: 1056 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.013
DANN	Benign	0.56
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs274883; hg19: chr19-48622545; COSMIC: COSV54392539; COSMIC: COSV54392539;