rs3730912

Variant names:

• chr19-48149578-G-T
• rs3730912
• NM_000234.3:c.776+185C>A

Variant summary

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

The NM_000234.3(LIG1):​c.776+185C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,154 control chromosomes in the GnomAD database, including 2,167 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 0.16 (2167 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0600
• Publications: 9 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)

LIG1-AS1 (HGNC:58602):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.776+185C>A		intron_variant	Intron 9 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.776+185C>A		intron_variant	Intron 9 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23683 AN: 152036 Hom.: 2166 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0829

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.156 AC: 23703 AN: 152154 Hom.: 2167 Cov.: 32 AF XY: 0.152 AC XY: 11311 AN XY: 74374

African (AFR) AF: 0.264 AC: 10955 AN: 41518

American (AMR) AF: 0.138 AC: 2109 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 336 AN: 3468

East Asian (EAS) AF: 0.121 AC: 627 AN: 5170

South Asian (SAS) AF: 0.0825 AC: 398 AN: 4822

European-Finnish (FIN) AF: 0.0868 AC: 920 AN: 10598

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7985 AN: 67968

Other (OTH) AF: 0.134 AC: 282 AN: 2110

Alfa AF: 0.147 Hom.: 264

Bravo AF: 0.166

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.90
DANN	Benign	0.61
PhyloP100		-0.060
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: rs3730912; hg19: chr19-48652835;