19-48115454-A-G

Variant names:

• chr19-48115454-A-G
• rs251692
• ENST00000594759.5:n.*1552T>C

Variant summary

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

The ENST00000594759.5(LIG1):​n.*1552T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 608,618 control chromosomes in the GnomAD database, including 110,911 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 0.64 (32691 hom., cov: 32)
  • Exomes 𝑓: 0.58 (78220 hom.)
• Consequence: LIG1 ENST00000594759.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000594759.5. 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.*195T>C		3_prime_UTR	Exon 28 of 28	NP_000225.1
	LIG1	NR_110296.2		n.4116T>C		non_coding_transcript_exon	Exon 28 of 28
	LIG1	NR_135497.2		n.4119T>C		non_coding_transcript_exon	Exon 28 of 28

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000594759.5	TSL:1	n.*1552T>C		non_coding_transcript_exon	Exon 28 of 28	ENSP00000471380.1
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.*195T>C		3_prime_UTR	Exon 28 of 28	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.*1552T>C		3_prime_UTR	Exon 28 of 28	ENSP00000471380.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97232 AN: 151942 Hom.: 32641 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.576 AC: 263176 AN: 456558 Hom.: 78220 Cov.: 3 AF XY: 0.573 AC XY: 138812 AN XY: 242160

African (AFR) AF: 0.851 AC: 11231 AN: 13194

American (AMR) AF: 0.528 AC: 13317 AN: 25230

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 7018 AN: 14528

East Asian (EAS) AF: 0.867 AC: 25994 AN: 29990

South Asian (SAS) AF: 0.550 AC: 27086 AN: 49252

European-Finnish (FIN) AF: 0.572 AC: 15964 AN: 27910

Middle Eastern (MID) AF: 0.556 AC: 1117 AN: 2010

European-Non Finnish (NFE) AF: 0.544 AC: 145990 AN: 268518

Other (OTH) AF: 0.596 AC: 15459 AN: 25926

GnomAD4 genome AF: 0.640 AC: 97337 AN: 152060 Hom.: 32691 Cov.: 32 AF XY: 0.637 AC XY: 47369 AN XY: 74332

African (AFR) AF: 0.847 AC: 35142 AN: 41506

American (AMR) AF: 0.543 AC: 8289 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 1675 AN: 3466

East Asian (EAS) AF: 0.869 AC: 4492 AN: 5170

South Asian (SAS) AF: 0.555 AC: 2671 AN: 4814

European-Finnish (FIN) AF: 0.583 AC: 6159 AN: 10566

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36964 AN: 67964

Other (OTH) AF: 0.616 AC: 1299 AN: 2108

Alfa AF: 0.477 Hom.: 1410

Bravo AF: 0.651

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.42
PhyloP100		-1.2
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: rs251692; hg19: chr19-48618711;