rs2304136

Variant names:

• chr19-48139867-T-C
• rs2304136
• NM_000234.3:c.1087+104A>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.1087+104A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 1,354,896 control chromosomes in the GnomAD database, including 10,713 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 0.17 (4045 hom., cov: 32)
  • Exomes 𝑓: 0.079 (6668 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.98
• Publications: 12 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.1087+104A>G		intron_variant	Intron 12 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.1087+104A>G		intron_variant	Intron 12 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26055 AN: 151992 Hom.: 4033 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.0790 AC: 95067 AN: 1202786 Hom.: 6668 AF XY: 0.0803 AC XY: 49024 AN XY: 610664

African (AFR) AF: 0.432 AC: 12401 AN: 28682

American (AMR) AF: 0.0920 AC: 4085 AN: 44382

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 2098 AN: 24612

East Asian (EAS) AF: 0.203 AC: 7807 AN: 38540

South Asian (SAS) AF: 0.148 AC: 11902 AN: 80590

European-Finnish (FIN) AF: 0.0673 AC: 3080 AN: 45750

Middle Eastern (MID) AF: 0.163 AC: 866 AN: 5302

European-Non Finnish (NFE) AF: 0.0537 AC: 47400 AN: 882812

Other (OTH) AF: 0.104 AC: 5428 AN: 52116

GnomAD4 genome AF: 0.172 AC: 26097 AN: 152110 Hom.: 4045 Cov.: 32 AF XY: 0.169 AC XY: 12591 AN XY: 74366

African (AFR) AF: 0.414 AC: 17169 AN: 41450

American (AMR) AF: 0.118 AC: 1807 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 308 AN: 3470

East Asian (EAS) AF: 0.193 AC: 999 AN: 5164

South Asian (SAS) AF: 0.148 AC: 712 AN: 4824

European-Finnish (FIN) AF: 0.0664 AC: 704 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0571 AC: 3886 AN: 68018

Other (OTH) AF: 0.150 AC: 316 AN: 2108

Alfa AF: 0.0782 Hom.: 1428

Bravo AF: 0.186

Asia WGS AF: 0.175 AC: 610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.022
DANN	Benign	0.38
PhyloP100		-4.0
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: rs2304136; hg19: chr19-48643124; COSMIC: COSV54390221; COSMIC: COSV54390221;