Genetic Variant SFSWAP:p.Leu667Leu (chr12-131766167-G-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0250

Publications

14 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFSWAP	NM_004592.4 link	c.2001G>C	p.Leu667Leu	synonymous_variant	Exon 13 of 18	ENST00000261674.9	NP_004583.2	Q12872-1Q8IV81

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFSWAP	ENST00000261674.9 link	c.2001G>C	p.Leu667Leu	synonymous_variant	Exon 13 of 18	1	NM_004592.4	ENSP00000261674.4		Q12872-1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26794

AN:

152042

Hom.:

3090

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.236

AC XY:

171295

AN XY:

727078

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

13569

27138

40706

54275

67844

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9730

19460

29190

38920

48650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.176

AC:

26801

AN:

152160

Hom.:

3089

Cov.:

AF XY:

0.174

AC XY:

12904

AN XY:

74366

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.253

AC:

17229

AN:

67996

Other (OTH)

AF:

0.197

AC:

416

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

1126

2253

3379

4506

5632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

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)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over