rs274860

Positions:

• chr19-48154363-G-A
• chr19-48154363-G-C

Variant summary

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

The NM_000234.3(LIG1):​c.371-396C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0959 in 304,542 control chromosomes in the GnomAD database, including 2,658 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 0.12 (2068 hom., cov: 30)
  • Exomes 𝑓: 0.067 (590 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.471

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3	c.371-396C>T		intron_variant		ENST00000263274.12	NP_000225.1
LOC107985293	XR_007067281.1	n.178-979G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.371-396C>T		intron_variant		1	NM_000234.3	ENSP00000263274	P4

Frequencies

GnomAD3 genomes AF: 0.125 AC: 18907 AN: 151574 Hom.: 2069 Cov.: 30

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0853

Gnomad ASJ AF: 0.0631

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0649

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0420

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.0672 AC: 10278 AN: 152850 Hom.: 590 Cov.: 0 AF XY: 0.0686 AC XY: 5609 AN XY: 81776

Gnomad4 AFR exome AF: 0.295

Gnomad4 AMR exome AF: 0.0698

Gnomad4 ASJ exome AF: 0.0621

Gnomad4 EAS exome AF: 0.170

Gnomad4 SAS exome AF: 0.0908

Gnomad4 FIN exome AF: 0.0563

Gnomad4 NFE exome AF: 0.0384

Gnomad4 OTH exome AF: 0.0687

GnomAD4 genome AF: 0.125 AC: 18932 AN: 151692 Hom.: 2068 Cov.: 30 AF XY: 0.125 AC XY: 9247 AN XY: 74084

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.0850

Gnomad4 ASJ AF: 0.0631

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0649

Gnomad4 NFE AF: 0.0420

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0500 Hom.: 437

Bravo AF: 0.133

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.75

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: rs274860; hg19: chr19-48657620;