ENST00000594759.5:n.-7C>A

Variant names:

• chr19-48170333-G-T
• rs2123143157
• NM_000234.3:c.-150C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000594759.5(LIG1):​n.-150C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 289,700 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: LIG1 ENST00000594759.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.71
• 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: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).

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.-150C>A		5_prime_UTR	Exon 1 of 28	NP_000225.1
	LIG1	NM_001320970.2		c.-150C>A		5_prime_UTR	Exon 1 of 28	NP_001307899.1
	LIG1	NM_001320971.2		c.-150C>A		5_prime_UTR	Exon 1 of 27	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.-150C>A		5_prime_UTR	Exon 1 of 28	ENSP00000263274.6
	LIG1	ENST00000916675.1		c.-150C>A		5_prime_UTR	Exon 1 of 28	ENSP00000586734.1
	LIG1	ENST00000916664.1		c.-148C>A		5_prime_UTR	Exon 1 of 28	ENSP00000586723.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000345 AC: 1 AN: 289700 Hom.: 0 Cov.: 0 AF XY: 0.00000606 AC XY: 1 AN XY: 164964

African (AFR) AF: 0.00 AC: 0 AN: 6518

American (AMR) AF: 0.00 AC: 0 AN: 26426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10142

East Asian (EAS) AF: 0.00 AC: 0 AN: 7782

South Asian (SAS) AF: 0.0000171 AC: 1 AN: 58546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12140

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 152002

Other (OTH) AF: 0.00 AC: 0 AN: 13478

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	21
DANN	Benign	0.95
PhyloP100		2.7
PromoterAI		0.0067	Neutral

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: rs2123143157; hg19: chr19-48673590;