rs12933120

chr16-3584745-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.625

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4	c.4739+24G>T		intron_variant		ENST00000294008.4
SLX4	XM_011522715.4	c.4736+24G>T		intron_variant
SLX4	XM_024450471.2	c.4739+24G>T		intron_variant
SLX4	XM_047434801.1	c.3737+24G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4	c.4739+24G>T		intron_variant		5	NM_032444.4	P1

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13976 AN: 152184 Hom.: 897 Cov.: 32

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

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.: 24 AF XY: 0.127 AC XY: 89478 AN XY: 706046

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.: 32 AF XY: 0.0888 AC XY: 6611 AN XY: 74472

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:2

Revision: criteria provided, single submitter

Submissions by phenotype

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 10, 2019

- -

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

Other links and lift over

dbSNP: rs12933120; hg19: chr16-3634746;