rs149916101

Variant names:

• chr16-3595723-C-T
• rs149916101
• NM_032444.4:c.1925-30G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-3595723-C-T
• chr16-3595723-C-A
• chr16-3595723-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_032444.4(SLX4):​c.1925-30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,609,636 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (11 hom.)
• Consequence: SLX4 NM_032444.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.04
• Publications: 1 publications found

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: ClinGen, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• familial ovarian cancer

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-3595723-C-T is Benign according to our data. Variant chr16-3595723-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262039.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00626 (954/152298) while in subpopulation AFR AF = 0.0176 (733/41568). AF 95% confidence interval is 0.0166. There are 9 homozygotes in GnomAd4. There are 459 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032444.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	NM_032444.4	MANE Select	c.1925-30G>A		intron	N/A	NP_115820.2	Q8IY92-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLX4	ENST00000294008.4	TSL:5 MANE Select	c.1925-30G>A		intron	N/A	ENSP00000294008.3	Q8IY92-1
	SLX4	ENST00000466154.5	TSL:1	n.3146-30G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00623 AC: 948 AN: 152180 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00175

Gnomad OTH AF: 0.00669

GnomAD2 exomes AF: 0.00302 AC: 731 AN: 241944 AF XY: 0.00273

Gnomad AFR exome AF: 0.0170

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.00162

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000490

Gnomad NFE exome AF: 0.00198

Gnomad OTH exome AF: 0.00391

GnomAD4 exome AF: 0.00206 AC: 2998 AN: 1457338 Hom.: 11 Cov.: 31 AF XY: 0.00208 AC XY: 1508 AN XY: 724998

African (AFR) AF: 0.0175 AC: 585 AN: 33360

American (AMR) AF: 0.00400 AC: 178 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00130 AC: 34 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.00324 AC: 279 AN: 86054

European-Finnish (FIN) AF: 0.000287 AC: 15 AN: 52202

Middle Eastern (MID) AF: 0.0129 AC: 74 AN: 5756

European-Non Finnish (NFE) AF: 0.00148 AC: 1638 AN: 1109706

Other (OTH) AF: 0.00324 AC: 195 AN: 60106

GnomAD4 genome AF: 0.00626 AC: 954 AN: 152298 Hom.: 9 Cov.: 32 AF XY: 0.00616 AC XY: 459 AN XY: 74464

African (AFR) AF: 0.0176 AC: 733 AN: 41568

American (AMR) AF: 0.00418 AC: 64 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00353 AC: 17 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00175 AC: 119 AN: 68020

Other (OTH) AF: 0.00662 AC: 14 AN: 2114

Alfa AF: 0.00144 Hom.: 0

Bravo AF: 0.00654

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
DANN	Benign	0.54
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149916101; hg19: chr16-3645724;