NM_000234.3:c.2676+11G>C

Variant names:

• chr19-48115862-C-G
• rs1232042683
• NM_000234.3:c.2676+11G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_000234.3(LIG1):​c.2676+11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.98
• Publications: 0 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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 19-48115862-C-G is Benign according to our data. Variant chr19-48115862-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2822728.Status of the report is criteria_provided_single_submitter, 1 stars.

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.2676+11G>C		intron	N/A	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.2673+11G>C		intron	N/A	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.2586+11G>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.2676+11G>C		intron	N/A	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.*1273+11G>C		intron	N/A	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000916675.1		c.2778+11G>C		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.20
DANN	Benign	0.66
PhyloP100		-4.0

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: rs1232042683; hg19: chr19-48619119;