rs3731027

Variant names:

• chr19-48121269-G-A
• rs3731027
• NM_000234.3:c.2286C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-48121269-G-A
• chr19-48121269-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000234.3(LIG1):​c.2286C>T​(p.Ile762Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,613,348 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (58 hom.)
• Consequence: LIG1 NM_000234.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.634
• Publications: 2 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

ENSG00000269534 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-48121269-G-A is Benign according to our data. Variant chr19-48121269-G-A is described in ClinVar as Benign. ClinVar VariationId is 784835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.634 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	NM_000234.3	MANE Select	c.2286C>T	p.Ile762Ile	synonymous	Exon 24 of 28	NP_000225.1	P18858-1
	LIG1	NM_001320970.2		c.2283C>T	p.Ile761Ile	synonymous	Exon 24 of 28	NP_001307899.1	A0A8V8TQC4
	LIG1	NM_001320971.2		c.2196C>T	p.Ile732Ile	synonymous	Exon 23 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.2286C>T	p.Ile762Ile	synonymous	Exon 24 of 28	ENSP00000263274.6	P18858-1
	LIG1	ENST00000594759.5	TSL:1	n.2283C>T		non_coding_transcript_exon	Exon 24 of 28	ENSP00000471380.1	M0R0Q7
	LIG1	ENST00000916675.1		c.2388C>T	p.Ile796Ile	synonymous	Exon 24 of 28	ENSP00000586734.1

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2365 AN: 152118 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.0527

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00825

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0120

GnomAD2 exomes AF: 0.00429 AC: 1070 AN: 249222 AF XY: 0.00322

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000303

Gnomad OTH exome AF: 0.00279

GnomAD4 exome AF: 0.00177 AC: 2583 AN: 1461112 Hom.: 58 Cov.: 31 AF XY: 0.00153 AC XY: 1113 AN XY: 726834

African (AFR) AF: 0.0572 AC: 1914 AN: 33474

American (AMR) AF: 0.00428 AC: 191 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.000184 AC: 205 AN: 1111690

Other (OTH) AF: 0.00411 AC: 248 AN: 60370

GnomAD4 genome AF: 0.0155 AC: 2365 AN: 152236 Hom.: 61 Cov.: 32 AF XY: 0.0152 AC XY: 1130 AN XY: 74432

African (AFR) AF: 0.0525 AC: 2181 AN: 41530

American (AMR) AF: 0.00824 AC: 126 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.000471 AC: 32 AN: 68008

Other (OTH) AF: 0.0118 AC: 25 AN: 2114

Alfa AF: 0.00741 Hom.: 15

Bravo AF: 0.0180

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.3
DANN	Benign	0.82
PhyloP100		-0.63
Mutation Taster		=100/0	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: rs3731027; hg19: chr19-48624526;