NM_000234.3:c.-58+498A>C

Variant names:

• chr19-48169743-T-G
• rs3730842
• NM_000234.3:c.-58+498A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000234.3(LIG1):​c.-58+498A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.00010 (0 hom., cov: 20)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 6 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.-58+498A>C		intron	N/A	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.-58+498A>C		intron	N/A	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.-58+498A>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.-58+498A>C		intron	N/A	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.-58+498A>C		intron	N/A	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000916675.1		c.-58+498A>C		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 12 AN: 117702 Hom.: 0 Cov.: 20

Gnomad AFR AF: 0.0000924

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000280

Gnomad SAS AF: 0.000984

Gnomad FIN AF: 0.000333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000531

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 394 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 284

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 16

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 152

Other (OTH) AF: 0.00 AC: 0 AN: 14

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000102 AC: 12 AN: 117778 Hom.: 0 Cov.: 20 AF XY: 0.0000716 AC XY: 4 AN XY: 55898

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000922 AC: 3 AN: 32536

American (AMR) AF: 0.00 AC: 0 AN: 10618

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2882

East Asian (EAS) AF: 0.000280 AC: 1 AN: 3568

South Asian (SAS) AF: 0.000987 AC: 3 AN: 3040

European-Finnish (FIN) AF: 0.000333 AC: 2 AN: 6010

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 206

European-Non Finnish (NFE) AF: 0.0000531 AC: 3 AN: 56542

Other (OTH) AF: 0.00 AC: 0 AN: 1602

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 300

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.8
DANN	Benign	0.23
PhyloP100		-1.5
PromoterAI		-0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3730842; hg19: chr19-48673000;