dbSNP rs3730838: LIG1:c.-416C>T (chr19-48170599-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000596549.6(LIG1):c.-416C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00747 in 268,764 control chromosomes in the GnomAD database, including 50 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 0.013 ( 50 hom., cov: 31)

Exomes 𝑓: 0.00035 ( 0 hom. )

Consequence

LIG1
ENST00000596549.6 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

2 publications found

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]

LIG1 links:

ZSWIM9 (HGNC:34495): (zinc finger SWIM-type containing 9) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. [provided by Alliance of Genome Resources, Apr 2022]

ZSWIM9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0129 (1966/152228) while in subpopulation AFR AF = 0.0457 (1898/41540). AF 95% confidence interval is 0.044. There are 50 homozygotes in GnomAd4. There are 923 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
ZSWIM9	NM_199341.4 link	c.-125G>A	upstream_gene_variant	ENST00000614654.2	NP_955373.3	Q86XI8-2
ZSWIM9	XM_006723204.4 link	c.-358G>A	upstream_gene_variant		XP_006723267.1
ZSWIM9	XM_005259449.4 link	c.-767G>A	upstream_gene_variant		XP_005259506.1
ZSWIM9	XM_006723205.3 link	c.-121G>A	upstream_gene_variant		XP_006723268.1	Q86XI8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSWIM9	ENST00000614654.2 link	c.-125G>A		upstream_gene_variant		5	NM_199341.4	ENSP00000480314.1		Q86XI8-2
ZSWIM9	ENST00000328759.11 link	c.-125G>A		upstream_gene_variant		1		ENSP00000331363.7		Q86XI8-1

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1960

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0457

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00526

GnomAD4 exome

AF:

0.000352

AC:

AN:

116536

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

AN XY:

65540

show subpopulations

African (AFR)

AF:

0.0253

AC:

AN:

514

American (AMR)

AF:

0.00339

AC:

AN:

1476

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2378

East Asian (EAS)

AF:

0.00

AC:

AN:

528

South Asian (SAS)

AF:

0.000137

AC:

AN:

29296

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7492

Middle Eastern (MID)

AF:

0.00236

AC:

AN:

424

European-Non Finnish (NFE)

AF:

0.0000582

AC:

AN:

68704

Other (OTH)

AF:

0.00245

AC:

AN:

5724

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.526

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0129

AC:

1966

AN:

152228

Hom.:

Cov.:

AF XY:

0.0124

AC XY:

923

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.0457

AC:

1898

AN:

41540

American (AMR)

AF:

0.00320

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67998

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

173

260

346

433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0125

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

2.4

PromoterAI

-0.23

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over