chr19-48115454-A-G

Position:

• chr19-48115454-A-G

Variant summary

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

The NM_000234.3(LIG1):​c.*195T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 608,618 control chromosomes in the GnomAD database, including 110,911 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 0.64 (32691 hom., cov: 32)
  • Exomes 𝑓: 0.58 (78220 hom.)
• Consequence: LIG1 NM_000234.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIG1	NM_000234.3	c.*195T>C		3_prime_UTR_variant	28/28	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274	c.*195T>C		3_prime_UTR_variant	28/28	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97232 AN: 151942 Hom.: 32641 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.543

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.869

Gnomad SAS AF: 0.554

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.615

GnomAD4 exome AF: 0.576 AC: 263176 AN: 456558 Hom.: 78220 Cov.: 3 AF XY: 0.573 AC XY: 138812 AN XY: 242160

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.528

Gnomad4 ASJ exome AF: 0.483

Gnomad4 EAS exome AF: 0.867

Gnomad4 SAS exome AF: 0.550

Gnomad4 FIN exome AF: 0.572

Gnomad4 NFE exome AF: 0.544

Gnomad4 OTH exome AF: 0.596

GnomAD4 genome AF: 0.640 AC: 97337 AN: 152060 Hom.: 32691 Cov.: 32 AF XY: 0.637 AC XY: 47369 AN XY: 74332

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.869

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.583

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.616

Alfa AF: 0.444 Hom.: 1122

Bravo AF: 0.651

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.42

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: rs251692; hg19: chr19-48618711;