dbSNP rs2722963: SEMA3E:c.457-10229C>T (chr7-83428712-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012431.3(SEMA3E):c.457-10229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,974 control chromosomes in the GnomAD database, including 33,337 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 0.64 ( 33337 hom., cov: 32)

Consequence

SEMA3E
NM_012431.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.466

Publications

3 publications found

Variant links:

Genes affected

SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

SEMA3E Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Kallmann syndrome
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
CHARGE syndrome
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

SEMA3E links:

ENSG00000303211 (HGNC:):

ENSG00000303211 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3 link	c.457-10229C>T		intron_variant	Intron 4 of 16	ENST00000643230.2	NP_036563.1	O15041-1
SEMA3E	NM_001178129.2 link	c.277-10229C>T		intron_variant	Intron 4 of 16		NP_001171600.1	O15041-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 link	c.457-10229C>T		intron_variant	Intron 4 of 16		NM_012431.3	ENSP00000496491.1		O15041-1

Frequencies

GnomAD3 genomes

AF:

0.638

AC:

96816

AN:

151856

Hom.:

33323

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.805

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.996

Gnomad SAS

AF:

0.734

Gnomad FIN

AF:

0.796

Gnomad MID

AF:

0.579

Gnomad NFE

AF:

0.711

Gnomad OTH

AF:

0.661

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.637

AC:

96864

AN:

151974

Hom.:

33337

Cov.:

AF XY:

0.648

AC XY:

48133

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.371

AC:

15370

AN:

41398

American (AMR)

AF:

0.752

AC:

11486

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

2264

AN:

3466

East Asian (EAS)

AF:

0.996

AC:

5155

AN:

5176

South Asian (SAS)

AF:

0.735

AC:

3550

AN:

4828

European-Finnish (FIN)

AF:

0.796

AC:

8413

AN:

10572

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.711

AC:

48324

AN:

67950

Other (OTH)

AF:

0.663

AC:

1396

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1581

3162

4742

6323

7904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.667

Hom.:

6333

Bravo

AF:

0.624

Asia WGS

AF:

0.846

AC:

2931

AN:

3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

(source)

DANN

Benign

0.75

PhyloP100

-0.47

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over