Variant rs112226642 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032444.4(SLX4):c.2013+23G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 1,612,140 control chromosomes in the GnomAD database, including 3,408 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 320 hom., cov: 32)

Exomes 𝑓: 0.063 ( 3088 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.88

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BP6

Variant 16-3595582-C-T is Benign according to our data. Variant chr16-3595582-C-T is described in ClinVar as [Benign]. Clinvar id is 262041.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3595582-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0698 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLX4	NM_032444.4 linkuse as main transcript	c.2013+23G>A		intron_variant		ENST00000294008.4	NP_115820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.2013+23G>A		intron_variant		5	NM_032444.4	ENSP00000294008	P1	Q8IY92-1
SLX4	ENST00000466154.5 linkuse as main transcript			downstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0631

AC:

9597

AN:

152140

Hom.:

319

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0574

Gnomad AMI

AF:

0.0901

Gnomad AMR

AF:

0.0737

Gnomad ASJ

AF:

0.0187

Gnomad EAS

AF:

0.0364

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.0867

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0655

Gnomad OTH

AF:

0.0579

GnomAD3 exomes

AF:

0.0610

AC:

15149

AN:

248364

Hom.:

533

AF XY:

0.0597

AC XY:

8040

AN XY:

134686

show subpopulations

Gnomad AFR exome

AF:

0.0570

Gnomad AMR exome

AF:

0.0713

Gnomad ASJ exome

AF:

0.0190

Gnomad EAS exome

AF:

0.0347

Gnomad SAS exome

AF:

0.0519

Gnomad FIN exome

AF:

0.0873

Gnomad NFE exome

AF:

0.0645

Gnomad OTH exome

AF:

0.0527

GnomAD4 exome

AF:

0.0628

AC:

91725

AN:

1459882

Hom.:

3088

Cov.:

AF XY:

0.0621

AC XY:

45121

AN XY:

726298

show subpopulations

Gnomad4 AFR exome

AF:

0.0577

Gnomad4 AMR exome

AF:

0.0684

Gnomad4 ASJ exome

AF:

0.0189

Gnomad4 EAS exome

AF:

0.0315

Gnomad4 SAS exome

AF:

0.0533

Gnomad4 FIN exome

AF:

0.0826

Gnomad4 NFE exome

AF:

0.0651

Gnomad4 OTH exome

AF:

0.0591

GnomAD4 genome

AF:

0.0631

AC:

9605

AN:

152258

Hom.:

320

Cov.:

AF XY:

0.0641

AC XY:

4775

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0575

Gnomad4 AMR

AF:

0.0734

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0363

Gnomad4 SAS

AF:

0.0541

Gnomad4 FIN

AF:

0.0867

Gnomad4 NFE

AF:

0.0655

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0604

Hom.:

Bravo

AF:

0.0625

Asia WGS

AF:

0.0560

AC:

197

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Aug 31, 2012	Curator: Arleen D. Auerbach. Submitter to LOVD: Janine Bakker. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Fanconi anemia complementation group P

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.92

DANN

Benign

0.75

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over