rs1051233

Positions:

• chr12-131766167-G-C
• chr12-131766167-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004592.4(SFSWAP):​c.2001G>C​(p.Leu667Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 1,613,676 control chromosomes in the GnomAD database, including 47,557 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 0.18 (3089 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44468 hom.)
• Consequence: SFSWAP NM_004592.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250

Genes affected

SFSWAP (HGNC:10790): (splicing factor SWAP) This gene encodes a human homolog of Drosophila splicing regulatory protein. This gene autoregulates its expression by control of splicing of its first two introns. In addition, it also regulates the splicing of fibronectin and CD45 genes. Two transcript variants encoding different isoforms have been identified. [provided by RefSeq, May 2012]

SFSWAP (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-0.025 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFSWAP	NM_004592.4	c.2001G>C	p.Leu667Leu	synonymous_variant	13/18	ENST00000261674.9	NP_004583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9	c.2001G>C	p.Leu667Leu	synonymous_variant	13/18	1	NM_004592.4	ENSP00000261674.4

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26794 AN: 152042 Hom.: 3090 Cov.: 32

Gnomad AFR AF: 0.0465

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.197

GnomAD3 exomes AF: 0.192 AC: 48118 AN: 251206 Hom.: 5469 AF XY: 0.195 AC XY: 26416 AN XY: 135802

Gnomad AFR exome AF: 0.0401

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.250

Gnomad EAS exome AF: 0.000816

Gnomad SAS exome AF: 0.142

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.238 AC: 347303 AN: 1461516 Hom.: 44468 Cov.: 33 AF XY: 0.236 AC XY: 171295 AN XY: 727078

Gnomad4 AFR exome AF: 0.0357

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.000731

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.264

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.176 AC: 26801 AN: 152160 Hom.: 3089 Cov.: 32 AF XY: 0.174 AC XY: 12904 AN XY: 74366

Gnomad4 AFR AF: 0.0464

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.129

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.253

Gnomad4 OTH AF: 0.197

Alfa AF: 0.203 Hom.: 1196

Bravo AF: 0.173

Asia WGS AF: 0.0650 AC: 226 AN: 3478

EpiCase AF: 0.247

EpiControl AF: 0.252

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.8
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1051233; hg19: chr12-132250712;