rs1046956

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004186.5(SEMA3F):c.1507T>A(p.Leu503Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,613,054 control chromosomes in the GnomAD database, including 388,839 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.68 ( 35489 hom., cov: 30)

Exomes 𝑓: 0.69 ( 353350 hom. )

Consequence

SEMA3F
NM_004186.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.12

Publications

41 publications found

Variant links:

Genes affected

SEMA3F (HGNC:10728): (semaphorin 3F) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin loop and a C-terminal basic domain. This gene is expressed by the endothelial cells where it was found to act in an autocrine fashion to induce apoptosis, inhibit cell proliferation and survival, and function as an anti-tumorigenic agent. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]

SEMA3F links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.3264076E-7).

BP6

Variant 3-50185493-T-A is Benign according to our data. Variant chr3-50185493-T-A is described in ClinVar as Benign. ClinVar VariationId is 3059010.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3F	NM_004186.5 link	c.1507T>A	p.Leu503Met	missense_variant	Exon 14 of 19	ENST00000002829.8	NP_004177.3	Q13275-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEMA3F	ENST00000002829.8 link	c.1507T>A	p.Leu503Met	missense_variant	Exon 14 of 19	1	NM_004186.5	ENSP00000002829.3	Q13275-1
SEMA3F	ENST00000434342.5 link	c.1414T>A	p.Leu472Met	missense_variant	Exon 13 of 18	1		ENSP00000409859.1	Q13275-2
SEMA3F	ENST00000413852.5 link	c.1210T>A	p.Leu404Met	missense_variant	Exon 13 of 18	1		ENSP00000388931.1	C9JPG5
SEMA3F	ENST00000470737.1 link	n.*28T>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.679

AC:

102824

AN:

151432

Hom.:

35448

Cov.:

show subpopulations

Gnomad AFR

AF:

0.605

Gnomad AMI

AF:

0.720

Gnomad AMR

AF:

0.721

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.991

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.752

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.663

Gnomad OTH

AF:

0.673

GnomAD2 exomes

AF:

0.741

AC:

185863

AN:

250686

AF XY:

0.743

show subpopulations

Gnomad AFR exome

AF:

0.600

Gnomad AMR exome

AF:

0.818

Gnomad ASJ exome

AF:

0.688

Gnomad EAS exome

AF:

0.994

Gnomad FIN exome

AF:

0.752

Gnomad NFE exome

AF:

0.665

Gnomad OTH exome

AF:

0.705

GnomAD4 exome

AF:

0.691

AC:

1009592

AN:

1461506

Hom.:

353350

Cov.:

AF XY:

0.696

AC XY:

505668

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.601

AC:

20104

AN:

33474

American (AMR)

AF:

0.807

AC:

36054

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.693

AC:

18098

AN:

26126

East Asian (EAS)

AF:

0.997

AC:

39577

AN:

39696

South Asian (SAS)

AF:

0.877

AC:

75645

AN:

86234

European-Finnish (FIN)

AF:

0.749

AC:

40015

AN:

53398

Middle Eastern (MID)

AF:

0.668

AC:

3846

AN:

5760

European-Non Finnish (NFE)

AF:

0.661

AC:

734376

AN:

1111758

Other (OTH)

AF:

0.693

AC:

41877

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

16706

33412

50117

66823

83529

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19238

38476

57714

76952

96190

<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:

0.679

AC:

102918

AN:

151548

Hom.:

35489

Cov.:

AF XY:

0.688

AC XY:

50996

AN XY:

74070

show subpopulations

African (AFR)

AF:

0.605

AC:

24938

AN:

41190

American (AMR)

AF:

0.722

AC:

11004

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2436

AN:

3464

East Asian (EAS)

AF:

0.991

AC:

5095

AN:

5142

South Asian (SAS)

AF:

0.884

AC:

4262

AN:

4822

European-Finnish (FIN)

AF:

0.752

AC:

7927

AN:

10538

Middle Eastern (MID)

AF:

0.622

AC:

179

AN:

288

European-Non Finnish (NFE)

AF:

0.663

AC:

45007

AN:

67858

Other (OTH)

AF:

0.677

AC:

1418

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1707

3413

5120

6826

8533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

812

1624

2436

3248

4060

<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:

0.668

Hom.:

10867

Bravo

AF:

0.668

TwinsUK

AF:

0.660

AC:

2447

ALSPAC

AF:

0.651

AC:

2509

ESP6500AA

AF:

0.600

AC:

2645

ESP6500EA

AF:

0.651

AC:

5598

ExAC

AF:

0.737

AC:

89460

Asia WGS

AF:

0.915

AC:

3180

AN:

3478

EpiCase

AF:

0.662

EpiControl

AF:

0.656

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3F-related disorder

Benign:1

Apr 11, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.80

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.094

DEOGEN2

Benign

0.0072

T;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.12

T;T;T

MetaRNN

Benign

6.3e-7

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.26

.;N;.

PhyloP100

1.1

PrimateAI

Benign

0.31

PROVEAN

Benign

0.56

N;N;N

REVEL

Benign

0.038

Sift

Benign

0.73

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.013

.;B;.

Vest4

0.059

MPC

0.78

ClinPred

0.000013

GERP RS

0.29

Varity_R

0.025

gMVP

0.068

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over