Variant rs12933120 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.4739+24G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,565,730 control chromosomes in the GnomAD database, including 13,336 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 900 hom., cov: 32)

Exomes 𝑓: 0.13 ( 12436 hom. )

Consequence

SLX4
NM_032444.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.625

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 16-3584745-C-A is Benign according to our data. Variant chr16-3584745-C-A is described in ClinVar as [Benign]. Clinvar id is 929612.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-3584745-C-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SLX4	NM_032444.4 linkuse as main transcript	c.4739+24G>T	intron_variant	ENST00000294008.4	NP_115820.2
SLX4	XM_011522715.4 linkuse as main transcript	c.4736+24G>T	intron_variant		XP_011521017.1
SLX4	XM_024450471.2 linkuse as main transcript	c.4739+24G>T	intron_variant		XP_024306239.1
SLX4	XM_047434801.1 linkuse as main transcript	c.3737+24G>T	intron_variant		XP_047290757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLX4	ENST00000294008.4 linkuse as main transcript	c.4739+24G>T		intron_variant		5	NM_032444.4	ENSP00000294008	P1	Q8IY92-1

Frequencies

GnomAD3 genomes

AF:

0.0918

AC:

13976

AN:

152184

Hom.:

897

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.148

Gnomad AMR

AF:

0.0843

Gnomad ASJ

AF:

0.139

Gnomad EAS

AF:

0.00520

Gnomad SAS

AF:

0.0950

Gnomad FIN

AF:

0.0811

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.139

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.101

AC:

25388

AN:

251464

Hom.:

1664

AF XY:

0.106

AC XY:

14431

AN XY:

135914

show subpopulations

Gnomad AFR exome

AF:

0.0219

Gnomad AMR exome

AF:

0.0592

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.00261

Gnomad SAS exome

AF:

0.105

Gnomad FIN exome

AF:

0.0834

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.116

GnomAD4 exome

AF:

0.127

AC:

179657

AN:

1413428

Hom.:

12436

Cov.:

AF XY:

0.127

AC XY:

89478

AN XY:

706046

show subpopulations

Gnomad4 AFR exome

AF:

0.0203

Gnomad4 AMR exome

AF:

0.0636

Gnomad4 ASJ exome

AF:

0.145

Gnomad4 EAS exome

AF:

0.00129

Gnomad4 SAS exome

AF:

0.102

Gnomad4 FIN exome

AF:

0.0879

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.119

GnomAD4 genome

AF:

0.0918

AC:

13975

AN:

152302

Hom.:

900

Cov.:

AF XY:

0.0888

AC XY:

6611

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0249

Gnomad4 AMR

AF:

0.0842

Gnomad4 ASJ

AF:

0.139

Gnomad4 EAS

AF:

0.00521

Gnomad4 SAS

AF:

0.0955

Gnomad4 FIN

AF:

0.0811

Gnomad4 NFE

AF:

0.139

Gnomad4 OTH

AF:

0.105

Alfa

AF:

0.130

Hom.:

1422

Bravo

AF:

0.0879

Asia WGS

AF:

0.0390

AC:

134

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, no assertion criteria provided

curation

Leiden Open Variation Database

Aug 31, 2012

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.3

DANN

Benign

0.38

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

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