rs175628

Positions:

• chr19-48145922-A-G
• chr19-48145922-A-T

Variant summary

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

The NM_000234.3(LIG1):​c.777-1959T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,166 control chromosomes in the GnomAD database, including 8,858 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 0.33 (8856 hom., cov: 32)
  • Exomes 𝑓: 0.36 (2 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.777-1959T>C		intron_variant		ENST00000263274.12
LOC107985293	XR_007067281.1	n.26+40A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.777-1959T>C		intron_variant		1	NM_000234.3	P4
	ENST00000594589.1	n.15A>G		non_coding_transcript_exon_variant	1/2	5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50577 AN: 152006 Hom.: 8839 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.309

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.357 AC: 15 AN: 42 Hom.: 2 Cov.: 0 AF XY: 0.333 AC XY: 10 AN XY: 30

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.324

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.333 AC: 50643 AN: 152124 Hom.: 8856 Cov.: 32 AF XY: 0.335 AC XY: 24878 AN XY: 74354

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.321

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.345

Alfa AF: 0.341 Hom.: 1552

Bravo AF: 0.323

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.88

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: rs175628; hg19: chr19-48649179;