rs7246696

Variant names:

• chr19-48169955-T-C
• rs7246696
• NM_000234.3:c.-58+286A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000234.3(LIG1):​c.-58+286A>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 0.51 (14245 hom., cov: 16)
  • Exomes 𝑓: 0.40 (4100 hom.)
• Consequence: LIG1 NM_000234.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 96

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIG1	NM_000234.3	c.-58+286A>G		intron_variant	Intron 1 of 27	ENST00000263274.12	NP_000225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIG1	ENST00000263274.12	c.-58+286A>G		intron_variant	Intron 1 of 27	1	NM_000234.3	ENSP00000263274.6

Frequencies

GnomAD3 genomes AF: 0.514 AC: 60439 AN: 117562 Hom.: 14213 Cov.: 16

Gnomad AFR AF: 0.603

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.583

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.516

GnomAD4 exome AF: 0.403 AC: 21918 AN: 54358 Hom.: 4100 Cov.: 0 AF XY: 0.409 AC XY: 13291 AN XY: 32468

African (AFR) AF: 0.576 AC: 160 AN: 278

American (AMR) AF: 0.320 AC: 123 AN: 384

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 371 AN: 1096

East Asian (EAS) AF: 0.810 AC: 94 AN: 116

South Asian (SAS) AF: 0.414 AC: 7405 AN: 17890

European-Finnish (FIN) AF: 0.458 AC: 1402 AN: 3062

Middle Eastern (MID) AF: 0.333 AC: 54 AN: 162

European-Non Finnish (NFE) AF: 0.390 AC: 11346 AN: 29074

Other (OTH) AF: 0.419 AC: 963 AN: 2296

GnomAD4 genome AF: 0.514 AC: 60525 AN: 117676 Hom.: 14245 Cov.: 16 AF XY: 0.524 AC XY: 29040 AN XY: 55472

African (AFR) AF: 0.604 AC: 19461 AN: 32246

American (AMR) AF: 0.504 AC: 5082 AN: 10092

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1160 AN: 2858

East Asian (EAS) AF: 0.766 AC: 3259 AN: 4252

South Asian (SAS) AF: 0.499 AC: 1709 AN: 3424

European-Finnish (FIN) AF: 0.583 AC: 3551 AN: 6092

Middle Eastern (MID) AF: 0.517 AC: 93 AN: 180

European-Non Finnish (NFE) AF: 0.445 AC: 25023 AN: 56192

Other (OTH) AF: 0.517 AC: 829 AN: 1602

Alfa AF: 0.435 Hom.: 1883

Bravo AF: 0.460

Asia WGS AF: 0.597 AC: 2071 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.53
PhyloP100		-1.9
PromoterAI		0.029	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7246696; hg19: chr19-48673212; COSMIC: COSV108089600; COSMIC: COSV108089600;