rs7246512

chr19-48148745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000234.3(LIG1):c.776+1018C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 152,016 control chromosomes in the GnomAD database, including 9,589 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 0.30 (9589 hom., cov: 32)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.43

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]

LOC107985293 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.776+1018C>T		intron_variant		ENST00000263274.12
LOC107985293	XR_007067281.1	n.177+2627G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.776+1018C>T		intron_variant		1	NM_000234.3	P4

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46019 AN: 151896 Hom.: 9580 Cov.: 32

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.303 AC: 46069 AN: 152016 Hom.: 9589 Cov.: 32 AF XY: 0.299 AC XY: 22178 AN XY: 74292

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.269

Alfa AF: 0.228 Hom.: 1290

Bravo AF: 0.324

Asia WGS AF: 0.289 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.11
Dann	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs7246512; hg19: chr19-48652002;