rs3730838

Positions:

• chr19-48170599-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000596549.6(LIG1):​c.-416C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 268,764 control chromosomes in the GnomAD database, including 50 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 0.013 (50 hom., cov: 31)
  • Exomes 𝑓: 0.00035 (0 hom.)
• Consequence: LIG1 ENST00000596549.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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=-0.74).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0129 (1966/152228) while in subpopulation AFR AF= 0.0457 (1898/41540). AF 95% confidence interval is 0.044. There are 50 homozygotes in gnomad4. There are 923 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.48170599G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000596549.6	c.-416C>T		5_prime_UTR_variant	1/26	4		ENSP00000471861.2

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1960 AN: 152110 Hom.: 50 Cov.: 31

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.000352 AC: 41 AN: 116536 Hom.: 0 Cov.: 0 AF XY: 0.000397 AC XY: 26 AN XY: 65540

Gnomad4 AFR exome AF: 0.0253

Gnomad4 AMR exome AF: 0.00339

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000137

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000582

Gnomad4 OTH exome AF: 0.00245

GnomAD4 genome AF: 0.0129 AC: 1966 AN: 152228 Hom.: 50 Cov.: 31 AF XY: 0.0124 AC XY: 923 AN XY: 74426

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.0143

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	15
DANN	Benign	0.87

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: rs3730838; hg19: chr19-48673856;