NM_000234.3:c.776+1018C>T

Variant names:

• chr19-48148745-G-A
• rs7246512
• NM_000234.3:c.776+1018C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000234.3(LIG1):​c.776+1018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,016 control chromosomes in the GnomAD database, including 9,589 homozygotes. 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 0.30 (9589 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43
• Publications: 11 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

LIG1-AS1 (HGNC:58602):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 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.776+1018C>T		intron	N/A	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.773+1018C>T		intron	N/A	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.686+1018C>T		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.776+1018C>T		intron	N/A	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.773+1018C>T		intron	N/A	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000916675.1		c.776+1018C>T		intron	N/A	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46019 AN: 151896 Hom.: 9580 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 46069 AN: 152016 Hom.: 9589 Cov.: 32 AF XY: 0.299 AC XY: 22178 AN XY: 74292

African (AFR) AF: 0.597 AC: 24721 AN: 41430

American (AMR) AF: 0.247 AC: 3779 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 614 AN: 3468

East Asian (EAS) AF: 0.316 AC: 1630 AN: 5156

South Asian (SAS) AF: 0.229 AC: 1107 AN: 4824

European-Finnish (FIN) AF: 0.154 AC: 1624 AN: 10570

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11753 AN: 67970

Other (OTH) AF: 0.269 AC: 567 AN: 2108

Alfa AF: 0.236 Hom.: 1434

Bravo AF: 0.324

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.58
PhyloP100		-3.4
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: rs7246512; hg19: chr19-48652002;