rs74747924

chr19-48169911-T-Cchr19-48169911-T-G

Variant summary

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

The NM_000234.3(LIG1):c.-58+330A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.011 (13 hom., cov: 10)
  • Exomes 𝑓: 0.00043 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (779/73034) while in subpopulation AFR AF= 0.0278 (425/15284). AF 95% confidence interval is 0.0256. There are 13 homozygotes in gnomad4. There are 380 alleles in male gnomad4 subpopulation. Median coverage is 10. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIG1	NM_000234.3	c.-58+330A>G		intron_variant		ENST00000263274.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIG1	ENST00000263274.12	c.-58+330A>G		intron_variant		1	NM_000234.3	P4

Frequencies

GnomAD3 genomes AF: 0.0106 AC: 774 AN: 72984 Hom.: 13 Cov.: 10

Gnomad AFR AF: 0.0276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00855

Gnomad ASJ AF: 0.0225

Gnomad EAS AF: 0.00791

Gnomad SAS AF: 0.00660

Gnomad FIN AF: 0.00779

Gnomad MID AF: 0.0286

Gnomad NFE AF: 0.00440

Gnomad OTH AF: 0.00696

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000431 AC: 3 AN: 6958 Hom.: 0 Cov.: 0 AF XY: 0.000716 AC XY: 3 AN XY: 4188

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.000791

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0107 AC: 779 AN: 73034 Hom.: 13 Cov.: 10 AF XY: 0.0110 AC XY: 380 AN XY: 34490

Gnomad4 AFR AF: 0.0278

Gnomad4 AMR AF: 0.00854

Gnomad4 ASJ AF: 0.0225

Gnomad4 EAS AF: 0.00794

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.00779

Gnomad4 NFE AF: 0.00440

Gnomad4 OTH AF: 0.00688

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.7
Dann	Benign	0.39

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: rs74747924; hg19: chr19-48673168;