19-48145214-T-C

Variant names:

• chr19-48145214-T-C
• rs10500298
• NM_000234.3:c.777-1251A>G

Variant summary

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

The NM_000234.3(LIG1):​c.777-1251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 151,990 control chromosomes in the GnomAD database, including 7,990 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 (7990 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• Publications: 5 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.777-1251A>G		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.774-1251A>G		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.687-1251A>G		intron	N/A	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.777-1251A>G		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.774-1251A>G		intron	N/A	ENSP00000471380.1
	LIG1	ENST00000699868.1		c.777-1251A>G		intron	N/A	ENSP00000514664.1

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45890 AN: 151872 Hom.: 7985 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.282

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.302 AC: 45912 AN: 151990 Hom.: 7990 Cov.: 32 AF XY: 0.305 AC XY: 22620 AN XY: 74266

African (AFR) AF: 0.128 AC: 5302 AN: 41468

American (AMR) AF: 0.283 AC: 4325 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1089 AN: 3468

East Asian (EAS) AF: 0.552 AC: 2848 AN: 5156

South Asian (SAS) AF: 0.321 AC: 1545 AN: 4812

European-Finnish (FIN) AF: 0.430 AC: 4541 AN: 10556

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25201 AN: 67936

Other (OTH) AF: 0.328 AC: 692 AN: 2112

Alfa AF: 0.217 Hom.: 582

Bravo AF: 0.288

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.1
DANN	Benign	0.20
PhyloP100		-0.26
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: rs10500298; hg19: chr19-48648471;