rs4917916

Positions:

• chr10-100913535-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243770.2(SLF2):​c.*233G>A variant causes a 3 prime UTR 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_001243770.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLF2	NM_018121.4	c.140+285G>A		intron_variant		ENST00000238961.9	NP_060591.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLF2	ENST00000238961.9	c.140+285G>A		intron_variant		1	NM_018121.4	ENSP00000238961.3

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

Gnomad4 AFR exome AF: 0.370

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.573

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.177

Gnomad4 NFE exome AF: 0.202

Gnomad4 OTH exome AF: 0.239

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.245

Alfa AF: 0.221 Hom.: 1493

Bravo AF: 0.276

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	12
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs4917916; hg19: chr10-102673292;