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GeneBe

19-48115709-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000234.3(LIG1):c.2700A>G(p.Gln900=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00203 in 1,614,128 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

LIG1
NM_000234.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.121
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 19-48115709-T-C is Benign according to our data. Variant chr19-48115709-T-C is described in ClinVar as [Benign]. Clinvar id is 1164975.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.121 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1683/152298) while in subpopulation AFR AF= 0.0372 (1545/41566). AF 95% confidence interval is 0.0356. There are 36 homozygotes in gnomad4. There are 805 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LIG1NM_000234.3 linkuse as main transcriptc.2700A>G p.Gln900= synonymous_variant 28/28 ENST00000263274.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LIG1ENST00000263274.12 linkuse as main transcriptc.2700A>G p.Gln900= synonymous_variant 28/281 NM_000234.3 P4P18858-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0110
AC:
1677
AN:
152180
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0371
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00726
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00956
GnomAD3 exomes
AF:
0.00290
AC:
730
AN:
251394
Hom.:
15
AF XY:
0.00205
AC XY:
279
AN XY:
135882
show subpopulations
Gnomad AFR exome
AF:
0.0385
Gnomad AMR exome
AF:
0.00252
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00109
AC:
1594
AN:
1461830
Hom.:
19
Cov.:
30
AF XY:
0.000921
AC XY:
670
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0375
Gnomad4 AMR exome
AF:
0.00266
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000513
Gnomad4 OTH exome
AF:
0.00260
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0111
AC:
1683
AN:
152298
Hom.:
36
Cov.:
32
AF XY:
0.0108
AC XY:
805
AN XY:
74482
show subpopulations
Gnomad4 AFR
AF:
0.0372
Gnomad4 AMR
AF:
0.00725
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00946
Alfa
AF:
0.00568
Hom.:
11
Bravo
AF:
0.0131
Asia WGS
AF:
0.00173
AC:
6
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
Cadd
Benign
3.9
Dann
Benign
0.75
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1803907; hg19: chr19-48618966; API