rs1051233

Variant names:

• chr12-131766167-G-C
• rs1051233
• NM_004592.4:c.2001G>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate 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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.071).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004592.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFSWAP	NM_004592.4	MANE Select	c.2001G>C	p.Leu667Leu	synonymous	Exon 13 of 18	NP_004583.2
	SFSWAP	NM_001261411.2		c.2001G>C	p.Leu667Leu	synonymous	Exon 13 of 19	NP_001248340.1	Q12872-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFSWAP	ENST00000261674.9	TSL:1 MANE Select	c.2001G>C	p.Leu667Leu	synonymous	Exon 13 of 18	ENSP00000261674.4	Q12872-1
	SFSWAP	ENST00000541286.5	TSL:1	c.2001G>C	p.Leu667Leu	synonymous	Exon 13 of 19	ENSP00000437738.1	Q12872-2
	SFSWAP	ENST00000535236.5	TSL:1	n.5335G>C		non_coding_transcript_exon	Exon 11 of 12

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

GnomAD2 exomes AF: 0.192 AC: 48118 AN: 251206 AF XY: 0.195

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 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

African (AFR) AF: 0.0357 AC: 1195 AN: 33458

American (AMR) AF: 0.180 AC: 8053 AN: 44690

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 6392 AN: 26118

East Asian (EAS) AF: 0.000731 AC: 29 AN: 39698

South Asian (SAS) AF: 0.142 AC: 12229 AN: 86244

European-Finnish (FIN) AF: 0.219 AC: 11671 AN: 53402

Middle Eastern (MID) AF: 0.167 AC: 960 AN: 5762

European-Non Finnish (NFE) AF: 0.264 AC: 293190 AN: 1111758

Other (OTH) AF: 0.225 AC: 13584 AN: 60386

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

African (AFR) AF: 0.0464 AC: 1926 AN: 41520

American (AMR) AF: 0.218 AC: 3325 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 814 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5188

South Asian (SAS) AF: 0.129 AC: 620 AN: 4812

European-Finnish (FIN) AF: 0.211 AC: 2225 AN: 10568

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.253 AC: 17229 AN: 67996

Other (OTH) AF: 0.197 AC: 416 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.8
DANN	Benign	0.74
PhyloP100		-0.025
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051233; hg19: chr12-132250712; COSMIC: COSV108023620;