rs75762935

Variant names:

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.2160+50C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,581,086 control chromosomes in the GnomAD database, including 3,330 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 321 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3009 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.72

Publications

10 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=-0.91).

BP6

Variant 16-3594403-G-A is Benign according to our data. Variant chr16-3594403-G-A is described in ClinVar as Benign. ClinVar VariationId is 262042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.2160+50C>T		intron_variant	Intron 10 of 14	ENST00000294008.4	NP_115820.2	Q8IY92-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 link	c.2160+50C>T		intron_variant	Intron 10 of 14	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0630

AC:

9579

AN:

152012

Hom.:

320

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0574

Gnomad AMI

AF:

0.0879

Gnomad AMR

AF:

0.0733

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0365

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0865

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0569

GnomAD2 exomes

AF:

0.0603

AC:

12149

AN:

201410

AF XY:

0.0588

show subpopulations

Gnomad AFR exome

AF:

0.0576

Gnomad AMR exome

AF:

0.0696

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.0336

Gnomad FIN exome

AF:

0.0861

Gnomad NFE exome

AF:

0.0643

Gnomad OTH exome

AF:

0.0523

GnomAD4 exome

AF:

0.0628

AC:

89723

AN:

1428956

Hom.:

3009

Cov.:

AF XY:

0.0621

AC XY:

43947

AN XY:

707968

show subpopulations

African (AFR)

AF:

0.0575

AC:

1881

AN:

32722

American (AMR)

AF:

0.0662

AC:

2602

AN:

39332

Ashkenazi Jewish (ASJ)

AF:

0.0189

AC:

484

AN:

25572

East Asian (EAS)

AF:

0.0312

AC:

1185

AN:

37998

South Asian (SAS)

AF:

0.0533

AC:

4400

AN:

82602

European-Finnish (FIN)

AF:

0.0826

AC:

4229

AN:

51208

Middle Eastern (MID)

AF:

0.0292

AC:

133

AN:

4554

European-Non Finnish (NFE)

AF:

0.0651

AC:

71322

AN:

1095796

Other (OTH)

AF:

0.0589

AC:

3487

AN:

59172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4763

9525

14288

19050

23813

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2626

5252

7878

10504

13130

<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:

0.0630

AC:

9587

AN:

152130

Hom.:

321

Cov.:

AF XY:

0.0642

AC XY:

4775

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.0574

AC:

2383

AN:

41480

American (AMR)

AF:

0.0730

AC:

1115

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3472

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5172

South Asian (SAS)

AF:

0.0541

AC:

261

AN:

4824

European-Finnish (FIN)

AF:

0.0865

AC:

917

AN:

10602

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0655

AC:

4454

AN:

67982

Other (OTH)

AF:

0.0563

AC:

119

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

461

923

1384

1846

2307

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0608

Hom.:

Bravo

AF:

0.0624

Asia WGS

AF:

0.0560

AC:

195

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia complementation group P

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

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

-0.91

CADD

Benign

0.092

(source)

DANN

Benign

0.43

PhyloP100

-1.7

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