rs75146816

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.*721T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0499 in 153,480 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.050 ( 243 hom., cov: 33)

Exomes 𝑓: 0.052 ( 1 hom. )

Consequence

SLX4
NM_032444.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.47

Publications

5 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:

ENSG00000261938 (HGNC:):

ENSG00000261938 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=-0.93).

BP6

Variant 16-3581621-A-G is Benign according to our data. Variant chr16-3581621-A-G is described in ClinVar as [Benign]. Clinvar id is 319130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLX4	NM_032444.4 link	c.*721T>C	3_prime_UTR_variant	Exon 15 of 15	ENST00000294008.4	NP_115820.2	Q8IY92-1
SLX4	XM_024450471.2 link	c.*721T>C	3_prime_UTR_variant	Exon 15 of 15		XP_024306239.1
SLX4	XM_011522715.4 link	c.*721T>C	3_prime_UTR_variant	Exon 15 of 15		XP_011521017.1
SLX4	XM_047434801.1 link	c.*721T>C	3_prime_UTR_variant	Exon 11 of 11		XP_047290757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 link	c.*721T>C		3_prime_UTR_variant	Exon 15 of 15	5	NM_032444.4	ENSP00000294008.3		Q8IY92-1
ENSG00000261938	ENST00000573982.1 link	n.198+243A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.0500

AC:

7607

AN:

152208

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.0866

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0654

Gnomad OTH

AF:

0.0488

GnomAD4 exome

AF:

0.0520

AC:

AN:

1154

Hom.:

Cov.:

AF XY:

0.0476

AC XY:

AN XY:

630

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0370

AC:

AN:

108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.0766

AC:

AN:

248

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0490

AC:

AN:

714

Other (OTH)

AF:

0.0625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0499

AC:

7603

AN:

152326

Hom.:

243

Cov.:

AF XY:

0.0513

AC XY:

3824

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41576

American (AMR)

AF:

0.0679

AC:

1039

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0187

AC:

AN:

3470

East Asian (EAS)

AF:

0.0363

AC:

188

AN:

5184

South Asian (SAS)

AF:

0.0540

AC:

261

AN:

4830

European-Finnish (FIN)

AF:

0.0866

AC:

920

AN:

10628

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0654

AC:

4448

AN:

68016

Other (OTH)

AF:

0.0478

AC:

101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

386

772

1159

1545

1931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0606

Hom.:

Bravo

AF:

0.0466

Asia WGS

AF:

0.0510

AC:

178

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group P

Benign:1

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 provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.27

(source)

DANN

Benign

0.24

PhyloP100

-1.5

Mutation Taster

=99/1

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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rs75146816

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