rs10051931

Variant names:

• chr5-94665771-A-G
• rs10051931
• NM_032290.4:c.1369-90A>G

Variant summary

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

The NM_032290.4(SLF1):​c.1369-90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 1,144,236 control chromosomes in the GnomAD database, including 41,794 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 0.25 (5162 hom., cov: 32)
  • Exomes 𝑓: 0.26 (36632 hom.)
• Consequence: SLF1 NM_032290.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.448
• Publications: 14 publications found

Genes affected

SLF1 (HGNC:25408): (SMC5-SMC6 complex localization factor 1) 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 nucleoplasm and site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032290.4. 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
	SLF1	NM_032290.4	MANE Select	c.1369-90A>G		intron	N/A	NP_115666.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLF1	ENST00000265140.10	TSL:2 MANE Select	c.1369-90A>G		intron	N/A	ENSP00000265140.5
	SLF1	ENST00000466957.1	TSL:5	n.*186-136A>G		intron	N/A	ENSP00000430335.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38275 AN: 152050 Hom.: 5162 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0339

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.257

GnomAD4 exome AF: 0.262 AC: 260351 AN: 992068 Hom.: 36632 AF XY: 0.260 AC XY: 129391 AN XY: 496844

African (AFR) AF: 0.268 AC: 5839 AN: 21794

American (AMR) AF: 0.156 AC: 3840 AN: 24690

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 3342 AN: 18566

East Asian (EAS) AF: 0.0494 AC: 1590 AN: 32212

South Asian (SAS) AF: 0.164 AC: 9454 AN: 57504

European-Finnish (FIN) AF: 0.223 AC: 7412 AN: 33246

Middle Eastern (MID) AF: 0.213 AC: 815 AN: 3828

European-Non Finnish (NFE) AF: 0.287 AC: 217245 AN: 756444

Other (OTH) AF: 0.247 AC: 10814 AN: 43784

GnomAD4 genome AF: 0.252 AC: 38288 AN: 152168 Hom.: 5162 Cov.: 32 AF XY: 0.243 AC XY: 18087 AN XY: 74408

African (AFR) AF: 0.270 AC: 11204 AN: 41520

American (AMR) AF: 0.194 AC: 2970 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 604 AN: 3466

East Asian (EAS) AF: 0.0340 AC: 176 AN: 5182

South Asian (SAS) AF: 0.155 AC: 750 AN: 4826

European-Finnish (FIN) AF: 0.219 AC: 2320 AN: 10592

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.287 AC: 19527 AN: 67980

Other (OTH) AF: 0.255 AC: 537 AN: 2108

Alfa AF: 0.271 Hom.: 6276

Bravo AF: 0.251

Asia WGS AF: 0.0940 AC: 327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.2
DANN	Benign	0.72
PhyloP100		0.45
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: rs10051931; hg19: chr5-94001476; COSMIC: COSV107308728;