rs35100567

Variant names:

• chr19-48115897-C-T
• rs35100567
• NM_000234.3:c.2652G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-48115897-C-T
• chr19-48115897-C-A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_000234.3(LIG1):​c.2652G>A​(p.Pro884Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,613,912 control chromosomes in the GnomAD database, including 157 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (10 hom., cov: 32)
  • Exomes 𝑓: 0.012 (147 hom.)
• Consequence: LIG1 NM_000234.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.49
• Publications: 7 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: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-48115897-C-T is Benign according to our data. Variant chr19-48115897-C-T is described in ClinVar as Benign. ClinVar VariationId is 1169235.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.2652G>A	p.Pro884Pro	synonymous	Exon 27 of 28	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.2649G>A	p.Pro883Pro	synonymous	Exon 27 of 28	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.2562G>A	p.Pro854Pro	synonymous	Exon 26 of 27	NP_001307900.1	A0A8V8TPH8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.2652G>A	p.Pro884Pro	synonymous	Exon 27 of 28	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.*1249G>A		non_coding_transcript_exon	Exon 27 of 28	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000594759.5	TSL:1	n.*1249G>A		3_prime_UTR	Exon 27 of 28	ENSP00000471380.1	M0R0Q7

Frequencies

GnomAD3 genomes AF: 0.00955 AC: 1453 AN: 152142 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00952

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.00670

GnomAD2 exomes AF: 0.00989 AC: 2482 AN: 251040 AF XY: 0.0103

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.0132

Gnomad OTH exome AF: 0.00832

GnomAD4 exome AF: 0.0123 AC: 18037 AN: 1461652 Hom.: 147 Cov.: 31 AF XY: 0.0124 AC XY: 9025 AN XY: 727126

African (AFR) AF: 0.00185 AC: 62 AN: 33476

American (AMR) AF: 0.00201 AC: 90 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00413 AC: 108 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0105 AC: 909 AN: 86256

European-Finnish (FIN) AF: 0.0219 AC: 1167 AN: 53316

Middle Eastern (MID) AF: 0.00226 AC: 13 AN: 5748

European-Non Finnish (NFE) AF: 0.0135 AC: 15039 AN: 1111916

Other (OTH) AF: 0.0107 AC: 646 AN: 60382

GnomAD4 genome AF: 0.00954 AC: 1453 AN: 152260 Hom.: 10 Cov.: 32 AF XY: 0.00931 AC XY: 693 AN XY: 74432

African (AFR) AF: 0.00185 AC: 77 AN: 41566

American (AMR) AF: 0.00314 AC: 48 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00953 AC: 46 AN: 4826

European-Finnish (FIN) AF: 0.0204 AC: 216 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1029 AN: 68018

Other (OTH) AF: 0.00663 AC: 14 AN: 2112

Alfa AF: 0.0114 Hom.: 27

Bravo AF: 0.00745

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.0127

EpiControl AF: 0.0109

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.27
DANN	Benign	0.62
PhyloP100		-2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Mutation Taster		=99/1	polymorphism

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: rs35100567; hg19: chr19-48619154;