rs4917916

Variant names:

• chr10-100913535-G-A
• rs4917916
• NM_018121.4:c.140+285G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018121.4(SLF2):​c.140+285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,244,492 control chromosomes in the GnomAD database, including 34,576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.26 (5863 hom., cov: 33)
  • Exomes 𝑓: 0.22 (28713 hom.)
• Consequence: SLF2 NM_018121.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• Publications: 11 publications found

Genes affected

SLF2 (HGNC:17814): (SMC5-SMC6 complex localization factor 2) Enables ubiquitin protein ligase binding activity. Involved in several processes, including positive regulation of cellular component organization; positive regulation of double-strand break repair; and protein localization to site of double-strand break. Located in chromatin; nucleoplasm; and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

SLF2 Gene-Disease associations (from GenCC):

• Atelis syndrome 1

  Inheritance: AR Classification: MODERATE Submitted by: G2P, Ambry Genetics

ENSG00000272572 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018121.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	NM_018121.4	MANE Select	c.140+285G>A		intron	N/A	NP_060591.3
	SLF2	NM_001243770.2		c.*233G>A		3_prime_UTR	Exon 1 of 1	NP_001230699.1
	SLF2	NM_001136123.2		c.140+285G>A		intron	N/A	NP_001129595.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF2	ENST00000238961.9	TSL:1 MANE Select	c.140+285G>A		intron	N/A	ENSP00000238961.3
	SLF2	ENST00000370269.3	TSL:1	c.140+285G>A		intron	N/A	ENSP00000359292.3
	SLF2	ENST00000370271.7	TSL:1	c.140+285G>A		intron	N/A	ENSP00000359294.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39513 AN: 152014 Hom.: 5854 Cov.: 33

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.218 AC: 238209 AN: 1092360 Hom.: 28713 Cov.: 32 AF XY: 0.219 AC XY: 113161 AN XY: 517600

African (AFR) AF: 0.370 AC: 8491 AN: 22922

American (AMR) AF: 0.323 AC: 3038 AN: 9406

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 2076 AN: 14546

East Asian (EAS) AF: 0.573 AC: 14820 AN: 25858

South Asian (SAS) AF: 0.318 AC: 8077 AN: 25438

European-Finnish (FIN) AF: 0.177 AC: 3803 AN: 21490

Middle Eastern (MID) AF: 0.208 AC: 610 AN: 2930

European-Non Finnish (NFE) AF: 0.202 AC: 186713 AN: 925586

Other (OTH) AF: 0.239 AC: 10581 AN: 44184

GnomAD4 genome AF: 0.260 AC: 39555 AN: 152132 Hom.: 5863 Cov.: 33 AF XY: 0.262 AC XY: 19515 AN XY: 74350

African (AFR) AF: 0.345 AC: 14324 AN: 41462

American (AMR) AF: 0.287 AC: 4385 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 498 AN: 3472

East Asian (EAS) AF: 0.561 AC: 2900 AN: 5168

South Asian (SAS) AF: 0.338 AC: 1633 AN: 4828

European-Finnish (FIN) AF: 0.171 AC: 1813 AN: 10588

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13292 AN: 67996

Other (OTH) AF: 0.245 AC: 518 AN: 2114

Alfa AF: 0.228 Hom.: 3306

Bravo AF: 0.276

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.71
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs4917916; hg19: chr10-102673292;