dbSNP rs35562367: SFSWAP:p.Val189Ile (chr12-131719498-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004592.4(SFSWAP):c.565G>A(p.Val189Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00549 in 1,613,996 control chromosomes in the GnomAD database, including 48 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V189F) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 44 hom. )

Consequence

SFSWAP
NM_004592.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.287

Publications

10 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0062130988).

BP6

Variant 12-131719498-G-A is Benign according to our data. Variant chr12-131719498-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2643601.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 665 AD gene.

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.565G>A	p.Val189Ile	missense	Exon 4 of 18	NP_004583.2
	SFSWAP	NM_001261411.2		c.565G>A	p.Val189Ile	missense	Exon 4 of 19	NP_001248340.1	Q12872-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFSWAP	ENST00000261674.9	TSL:1 MANE Select	c.565G>A	p.Val189Ile	missense	Exon 4 of 18	ENSP00000261674.4	Q12872-1
SFSWAP	ENST00000541286.5	TSL:1	c.565G>A	p.Val189Ile	missense	Exon 4 of 19	ENSP00000437738.1	Q12872-2
SFSWAP	ENST00000535236.5	TSL:1	n.3899G>A		non_coding_transcript_exon	Exon 2 of 12

Frequencies

GnomAD3 genomes

AF:

0.00439

AC:

667

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00104

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00634

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00485

AC:

1220

AN:

251482

AF XY:

0.00540

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.00169

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00785

Gnomad NFE exome

AF:

0.00563

Gnomad OTH exome

AF:

0.00472

GnomAD4 exome

AF:

0.00560

AC:

8188

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

4247

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33478

American (AMR)

AF:

0.00163

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0107

AC:

919

AN:

86252

European-Finnish (FIN)

AF:

0.00743

AC:

397

AN:

53418

Middle Eastern (MID)

AF:

0.00381

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00574

AC:

6387

AN:

1111918

Other (OTH)

AF:

0.00493

AC:

298

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

419

837

1256

1674

2093

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.00437

AC:

665

AN:

152208

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

347

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00103

AC:

AN:

41550

American (AMR)

AF:

0.00419

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.0104

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00633

AC:

AN:

10584

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00634

AC:

431

AN:

68004

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

107

143

179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00488

Hom.:

Bravo

AF:

0.00351

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.00204

AC:

ESP6500EA

AF:

0.00570

AC:

ExAC

AF:

0.00497

AC:

603

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.1

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.094

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.80

M_CAP

Benign

0.0044

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-0.58

PhyloP100

0.29

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.37

REVEL

Benign

0.031

Sift

Benign

0.59

Sift4G

Benign

0.74

Polyphen

0.012

Vest4

0.12

MVP

0.12

MPC

0.67

ClinPred

0.0058

GERP RS

-3.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.018

gMVP

0.075

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over