rs175628

Variant names:

• chr19-48145922-A-G
• rs175628
• NM_000234.3:c.777-1959T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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)

ENSG00000269321 (HGNC:58602):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000234.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.777-1959T>C		intron	N/A	NP_000225.1
	LIG1	NM_001320970.2		c.774-1959T>C		intron	N/A	NP_001307899.1
	LIG1	NM_001320971.2		c.687-1959T>C		intron	N/A	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.777-1959T>C		intron	N/A	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.774-1959T>C		intron	N/A	ENSP00000471380.1
	ENSG00000269321	ENST00000594589.1	TSL:5	n.15A>G		non_coding_transcript_exon	Exon 1 of 2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.324 AC: 11 AN: 34

Other (OTH) AF: 1.00 AC: 2 AN: 2

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

African (AFR) AF: 0.235 AC: 9776 AN: 41520

American (AMR) AF: 0.297 AC: 4537 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1090 AN: 3470

East Asian (EAS) AF: 0.550 AC: 2842 AN: 5166

South Asian (SAS) AF: 0.321 AC: 1548 AN: 4816

European-Finnish (FIN) AF: 0.429 AC: 4536 AN: 10572

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25216 AN: 67982

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.337 Hom.: 1576

Bravo AF: 0.323

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.3
DANN	Benign	0.88
PhyloP100		-0.44
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: rs175628; hg19: chr19-48649179;