rs80186343

chr16-3595468-C-G

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.2013+137G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 930,750 control chromosomes in the GnomAD database, including 1,934 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.072 (410 hom., cov: 32)
  • Exomes 𝑓: 0.059 (1524 hom.)
• Consequence: SLX4 NM_032444.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -1.34

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=-0.86).
• BP6: Variant 16-3595468-C-G is Benign according to our data. Variant chr16-3595468-C-G is described in ClinVar as [Benign]. Clinvar id is 929586.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr16-3595468-C-G is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLX4	NM_032444.4	c.2013+137G>C		intron_variant		ENST00000294008.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLX4	ENST00000294008.4	c.2013+137G>C		intron_variant		5	NM_032444.4	P1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10969 AN: 152128 Hom.: 407 Cov.: 32

Gnomad AFR AF: 0.0890

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.0759

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0364

Gnomad SAS AF: 0.0533

Gnomad FIN AF: 0.0868

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0656

Gnomad OTH AF: 0.0669

GnomAD4 exome AF: 0.0594 AC: 46205 AN: 778504 Hom.: 1524 AF XY: 0.0584 AC XY: 23695 AN XY: 405790

Gnomad4 AFR exome AF: 0.0842

Gnomad4 AMR exome AF: 0.0665

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.0306

Gnomad4 SAS exome AF: 0.0510

Gnomad4 FIN exome AF: 0.0781

Gnomad4 NFE exome AF: 0.0615

Gnomad4 OTH exome AF: 0.0578

GnomAD4 genome AF: 0.0721 AC: 10983 AN: 152246 Hom.: 410 Cov.: 32 AF XY: 0.0726 AC XY: 5403 AN XY: 74438

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.0363

Gnomad4 SAS AF: 0.0542

Gnomad4 FIN AF: 0.0868

Gnomad4 NFE AF: 0.0656

Gnomad4 OTH AF: 0.0662

Alfa AF: 0.0747 Hom.: 43

Bravo AF: 0.0731

Asia WGS AF: 0.0570 AC: 201 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

Feb 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.28
Dann	Benign	0.71

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: rs80186343; hg19: chr16-3645469;