rs28516461

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032444.4(SLX4):c.678C>T(p.His226His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 1,614,068 control chromosomes in the GnomAD database, including 3,877 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 1447 hom., cov: 32)

Exomes 𝑓: 0.030 ( 2430 hom. )

Consequence

SLX4
NM_032444.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.120

Publications

11 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 16-3606556-G-A is Benign according to our data. Variant chr16-3606556-G-A is described in ClinVar as Benign. ClinVar VariationId is 262057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
SLX4	NM_032444.4 link	c.678C>T	p.His226His	synonymous_variant	Exon 3 of 15	ENST00000294008.4	NP_115820.2
SLX4	XM_024450471.2 link	c.678C>T	p.His226His	synonymous_variant	Exon 3 of 15		XP_024306239.1
SLX4	XM_011522715.4 link	c.678C>T	p.His226His	synonymous_variant	Exon 3 of 15		XP_011521017.1
SLX4	XR_007064923.1 link	n.1327C>T		non_coding_transcript_exon_variant	Exon 3 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLX4	ENST00000294008.4 link	c.678C>T	p.His226His	synonymous_variant	Exon 3 of 15	5	NM_032444.4	ENSP00000294008.3
SLX4	ENST00000466154.5 link	n.973C>T		non_coding_transcript_exon_variant	Exon 2 of 7	1
SLX4	ENST00000486524.1 link	n.1306C>T		non_coding_transcript_exon_variant	Exon 3 of 4	2
SLX4	ENST00000697858.1 link	n.19C>T		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0889

AC:

13520

AN:

152064

Hom.:

1444

Cov.:

show subpopulations

Gnomad AFR

AF:

0.253

Gnomad AMI

AF:

0.0209

Gnomad AMR

AF:

0.0525

Gnomad ASJ

AF:

0.0366

Gnomad EAS

AF:

0.0457

Gnomad SAS

AF:

0.126

Gnomad FIN

AF:

0.0134

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0843

GnomAD2 exomes

AF:

0.0492

AC:

12359

AN:

251426

AF XY:

0.0493

show subpopulations

Gnomad AFR exome

AF:

0.260

Gnomad AMR exome

AF:

0.0270

Gnomad ASJ exome

AF:

0.0314

Gnomad EAS exome

AF:

0.0512

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.0141

Gnomad OTH exome

AF:

0.0379

GnomAD4 exome

AF:

0.0300

AC:

43897

AN:

1461888

Hom.:

2430

Cov.:

AF XY:

0.0321

AC XY:

23323

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.276

AC:

9237

AN:

33480

American (AMR)

AF:

0.0289

AC:

1292

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0314

AC:

821

AN:

26136

East Asian (EAS)

AF:

0.0482

AC:

1912

AN:

39700

South Asian (SAS)

AF:

0.123

AC:

10588

AN:

86258

European-Finnish (FIN)

AF:

0.0133

AC:

711

AN:

53420

Middle Eastern (MID)

AF:

0.0697

AC:

402

AN:

5768

European-Non Finnish (NFE)

AF:

0.0145

AC:

16173

AN:

1112006

Other (OTH)

AF:

0.0457

AC:

2761

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

2690

5380

8070

10760

13450

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

884

1768

2652

3536

4420

<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:

0.0890

AC:

13537

AN:

152180

Hom.:

1447

Cov.:

AF XY:

0.0890

AC XY:

6625

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.253

AC:

10481

AN:

41470

American (AMR)

AF:

0.0524

AC:

801

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0366

AC:

127

AN:

3466

East Asian (EAS)

AF:

0.0460

AC:

238

AN:

5176

South Asian (SAS)

AF:

0.125

AC:

602

AN:

4824

European-Finnish (FIN)

AF:

0.0134

AC:

142

AN:

10612

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0136

AC:

925

AN:

68030

Other (OTH)

AF:

0.0834

AC:

176

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

545

1090

1635

2180

2725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0448

Hom.:

1180

Bravo

AF:

0.0993

Asia WGS

AF:

0.105

AC:

363

AN:

3478

EpiCase

AF:

0.0181

EpiControl

AF:

0.0191

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:3

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 14, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Fanconi anemia

Benign:1

Feb 03, 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

-0.87

CADD

Benign

0.98

(source)

DANN

Benign

0.89

PhyloP100

-0.12

Mutation Taster

=100/0

polymorphism (auto)

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over