rs3786763

Variant names:

• chr19-48132445-G-A
• rs3786763
• NM_000234.3:c.1725+537C>T

Variant summary

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

The NM_000234.3(LIG1):​c.1725+537C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,808 control chromosomes in the GnomAD database, including 2,046 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 0.15 (2046 hom., cov: 29)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.1725+537C>T		intron_variant	Intron 18 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.1725+537C>T		intron_variant	Intron 18 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22946 AN: 151690 Hom.: 2039 Cov.: 29

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.126

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.151 AC: 22978 AN: 151808 Hom.: 2046 Cov.: 29 AF XY: 0.148 AC XY: 11007 AN XY: 74180

African (AFR) AF: 0.255 AC: 10535 AN: 41324

American (AMR) AF: 0.133 AC: 2025 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3466

East Asian (EAS) AF: 0.119 AC: 614 AN: 5154

South Asian (SAS) AF: 0.0804 AC: 387 AN: 4816

European-Finnish (FIN) AF: 0.0868 AC: 914 AN: 10536

Middle Eastern (MID) AF: 0.0753 AC: 22 AN: 292

European-Non Finnish (NFE) AF: 0.115 AC: 7843 AN: 67944

Other (OTH) AF: 0.125 AC: 264 AN: 2106

Alfa AF: 0.152 Hom.: 403

Bravo AF: 0.160

Asia WGS AF: 0.122 AC: 424 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		1.1
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: rs3786763; hg19: chr19-48635702;