19-48169910-T-C

Variant names:

• chr19-48169910-T-C
• rs75696040
• NM_000234.3:c.-58+331A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000263274.12(LIG1):​c.-58+331A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0052 (0 hom., cov: 16)
  • Exomes 𝑓: 0.00022 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIG1 ENST00000263274.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000263274.12. 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.-58+331A>G		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.-58+331A>G		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.-58+331A>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.-58+331A>G		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.-58+331A>G		intron	N/A	ENSP00000471380.1
	LIG1	ENST00000699868.1		c.-58+149A>G		intron	N/A	ENSP00000514664.1

Frequencies

GnomAD3 genomes AF: 0.00522 AC: 352 AN: 67428 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.00819

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00657

Gnomad ASJ AF: 0.00610

Gnomad EAS AF: 0.00853

Gnomad SAS AF: 0.00338

Gnomad FIN AF: 0.00523

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00360

Gnomad OTH AF: 0.00440

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000217 AC: 3 AN: 13852 Hom.: 0 Cov.: 0 AF XY: 0.000362 AC XY: 3 AN XY: 8298

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 58

American (AMR) AF: 0.00 AC: 0 AN: 74

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 300

East Asian (EAS) AF: 0.00 AC: 0 AN: 18

South Asian (SAS) AF: 0.000427 AC: 2 AN: 4680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 60

European-Non Finnish (NFE) AF: 0.000136 AC: 1 AN: 7378

Other (OTH) AF: 0.00 AC: 0 AN: 600

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00523 AC: 353 AN: 67486 Hom.: 0 Cov.: 16 AF XY: 0.00515 AC XY: 169 AN XY: 32826

African (AFR) AF: 0.00823 AC: 116 AN: 14090

American (AMR) AF: 0.00655 AC: 50 AN: 7628

Ashkenazi Jewish (ASJ) AF: 0.00610 AC: 12 AN: 1968

East Asian (EAS) AF: 0.00855 AC: 16 AN: 1872

South Asian (SAS) AF: 0.00339 AC: 7 AN: 2064

European-Finnish (FIN) AF: 0.00523 AC: 26 AN: 4968

Middle Eastern (MID) AF: 0.0135 AC: 2 AN: 148

European-Non Finnish (NFE) AF: 0.00359 AC: 120 AN: 33380

Other (OTH) AF: 0.00433 AC: 4 AN: 924

Alfa AF: 0.134 Hom.: 91

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.36
PhyloP100		-1.5
PromoterAI		0.0076	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: rs75696040; hg19: chr19-48673167;