chr19-48151296-G-C

Variant names:

• chr19-48151296-G-C
• rs20580
• NM_000234.3:c.510C>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000234.3(LIG1):​c.510C>G​(p.Ala170Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A170A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 29)
• Consequence: LIG1 NM_000234.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 39 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)

LIG1-AS1 (HGNC:58602):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP7: Synonymous conserved (PhyloP=0.13 with no splicing effect.

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.510C>G	p.Ala170Ala	synonymous	Exon 7 of 28	NP_000225.1
	LIG1	NM_001320970.2		c.507C>G	p.Ala169Ala	synonymous	Exon 7 of 28	NP_001307899.1
	LIG1	NM_001320971.2		c.420C>G	p.Ala140Ala	synonymous	Exon 6 of 27	NP_001307900.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIG1	ENST00000263274.12	TSL:1 MANE Select	c.510C>G	p.Ala170Ala	synonymous	Exon 7 of 28	ENSP00000263274.6
	LIG1	ENST00000594759.5	TSL:1	n.507C>G		non_coding_transcript_exon	Exon 7 of 28	ENSP00000471380.1
	LIG1	ENST00000699868.1		c.510C>G	p.Ala170Ala	synonymous	Exon 7 of 28	ENSP00000514664.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.9
DANN	Benign	0.35
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs20580; hg19: chr19-48654553;