rs1051219

Positions:

• chr12-131753205-C-T

Variant summary

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

The ENST00000261674.9(SFSWAP):​c.1164C>T​(p.Asp388=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 1,613,950 control chromosomes in the GnomAD database, including 54,946 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 (3391 hom., cov: 33)
  • Exomes 𝑓: 0.25 (51555 hom.)
• Consequence: SFSWAP ENST00000261674.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFSWAP	NM_004592.4	c.1164C>T	p.Asp388=	synonymous_variant	8/18	ENST00000261674.9	NP_004583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9	c.1164C>T	p.Asp388=	synonymous_variant	8/18	1	NM_004592.4	ENSP00000261674	P4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27946 AN: 152094 Hom.: 3391 Cov.: 33

Gnomad AFR AF: 0.0498

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.197 AC: 49561 AN: 251482 Hom.: 5885 AF XY: 0.201 AC XY: 27364 AN XY: 135920

Gnomad AFR exome AF: 0.0422

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.000815

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.212

Gnomad NFE exome AF: 0.270

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.255 AC: 372718 AN: 1461738 Hom.: 51555 Cov.: 38 AF XY: 0.253 AC XY: 183656 AN XY: 727182

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.262

Gnomad4 EAS exome AF: 0.000730

Gnomad4 SAS exome AF: 0.140

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.286

Gnomad4 OTH exome AF: 0.239

GnomAD4 genome AF: 0.184 AC: 27954 AN: 152212 Hom.: 3391 Cov.: 33 AF XY: 0.179 AC XY: 13297 AN XY: 74404

Gnomad4 AFR AF: 0.0497

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.205

Alfa AF: 0.245 Hom.: 4459

Bravo AF: 0.181

Asia WGS AF: 0.0680 AC: 239 AN: 3478

EpiCase AF: 0.269

EpiControl AF: 0.275

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.91
DANN	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1051219; hg19: chr12-132237750; COSMIC: COSV55520835; COSMIC: COSV55520835;