19-48115454-A-T

Variant names:

• chr19-48115454-A-T
• rs251692
• NM_000234.3:c.*195T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000234.3(LIG1):​c.*195T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIG1 NM_000234.3 3_prime_UTR
• 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

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.*195T>A		3_prime_UTR	Exon 28 of 28	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.*195T>A		3_prime_UTR	Exon 28 of 28	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.*195T>A		3_prime_UTR	Exon 27 of 27	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.*195T>A		3_prime_UTR	Exon 28 of 28	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.*1552T>A		non_coding_transcript_exon	Exon 28 of 28	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000594759.5	TSL:1	n.*1552T>A		3_prime_UTR	Exon 28 of 28	ENSP00000471380.1	M0R0Q7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 457088 Hom.: 0 Cov.: 3 AF XY: 0.00 AC XY: 0 AN XY: 242442

African (AFR) AF: 0.00 AC: 0 AN: 13198

American (AMR) AF: 0.00 AC: 0 AN: 25260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14556

East Asian (EAS) AF: 0.00 AC: 0 AN: 30008

South Asian (SAS) AF: 0.00 AC: 0 AN: 49264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27956

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2014

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 268866

Other (OTH) AF: 0.00 AC: 0 AN: 25966

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.48
DANN	Benign	0.56
PhyloP100		-1.2

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;