rs80116508

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.1163+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 1,611,776 control chromosomes in the GnomAD database, including 3,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.067 ( 358 hom., cov: 31)

Exomes 𝑓: 0.063 ( 3131 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.330

Publications

12 publications found

Variant links:

Genes affected

SLX4 (HGNC:23845): (SLX4 structure-specific endonuclease subunit) This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]

SLX4 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group P
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
familial ovarian cancer
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
hereditary breast carcinoma
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SLX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 16-3600969-G-A is Benign according to our data. Variant chr16-3600969-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0718 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.1163+10C>T		intron_variant	Intron 5 of 14	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLX4	ENST00000294008.4 link	c.1163+10C>T	intron_variant	Intron 5 of 14	5	NM_032444.4	ENSP00000294008.3	Q8IY92-1
SLX4	ENST00000466154.5 link	n.2384+10C>T	intron_variant	Intron 3 of 6	1
SLX4	ENST00000486524.1 link	n.2727C>T	non_coding_transcript_exon_variant	Exon 4 of 4	2
SLX4	ENST00000697858.1 link	n.514C>T	non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0669

AC:

10167

AN:

151930

Hom.:

357

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0705

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0757

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0367

Gnomad SAS

AF:

0.0528

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0656

Gnomad OTH

AF:

0.0598

GnomAD2 exomes

AF:

0.0621

AC:

15459

AN:

249084

AF XY:

0.0607

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.0717

Gnomad ASJ exome

AF:

0.0188

Gnomad EAS exome

AF:

0.0349

Gnomad FIN exome

AF:

0.0869

Gnomad NFE exome

AF:

0.0647

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0631

AC:

92103

AN:

1459728

Hom.:

3131

Cov.:

AF XY:

0.0623

AC XY:

45265

AN XY:

726222

show subpopulations

African (AFR)

AF:

0.0722

AC:

2414

AN:

33452

American (AMR)

AF:

0.0690

AC:

3085

AN:

44684

Ashkenazi Jewish (ASJ)

AF:

0.0188

AC:

492

AN:

26132

East Asian (EAS)

AF:

0.0319

AC:

1265

AN:

39694

South Asian (SAS)

AF:

0.0533

AC:

4595

AN:

86176

European-Finnish (FIN)

AF:

0.0829

AC:

4391

AN:

52968

Middle Eastern (MID)

AF:

0.0290

AC:

152

AN:

5234

European-Non Finnish (NFE)

AF:

0.0649

AC:

72080

AN:

1111098

Other (OTH)

AF:

0.0602

AC:

3629

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.422

Heterozygous variant carriers

4703

9406

14108

18811

23514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2642

5284

7926

10568

13210

<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:

0.0669

AC:

10176

AN:

152048

Hom.:

358

Cov.:

AF XY:

0.0678

AC XY:

5039

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.0705

AC:

2925

AN:

41462

American (AMR)

AF:

0.0754

AC:

1151

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.0366

AC:

189

AN:

5170

South Asian (SAS)

AF:

0.0537

AC:

259

AN:

4822

European-Finnish (FIN)

AF:

0.0867

AC:

916

AN:

10560

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0656

AC:

4459

AN:

67974

Other (OTH)

AF:

0.0591

AC:

125

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

490

980

1470

1960

2450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0463

Hom.:

Bravo

AF:

0.0668

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:4

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 23, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 31, 2012

Leiden Open Variation Database

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Fanconi anemia

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.19

(source)

DANN

Benign

0.58

PhyloP100

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over