Variant rs2245441 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_012431.3(SEMA3E):c.998+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,591,472 control chromosomes in the GnomAD database, including 289,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22328 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267328 hom. )

Consequence

SEMA3E
NM_012431.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.173

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 7-83405438-T-A is Benign according to our data. Variant chr7-83405438-T-A is described in ClinVar as [Benign]. Clinvar id is 260257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83405438-T-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3 linkuse as main transcript	c.998+12A>T		intron_variant		ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2 linkuse as main transcript	c.818+12A>T		intron_variant			NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	Effect	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 linkuse as main transcript	c.998+12A>T	intron_variant	NM_012431.3	ENSP00000496491	P1	O15041-1
SEMA3E	ENST00000642232.1 linkuse as main transcript	c.998+12A>T	intron_variant		ENSP00000494064
SEMA3E	ENST00000643441.1 linkuse as main transcript	n.983+12A>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.506

AC:

76792

AN:

151696

Hom.:

22313

Cov.:

show subpopulations

Gnomad AFR

AF:

0.206

Gnomad AMI

AF:

0.684

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.445

Gnomad EAS

AF:

0.848

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.598

Gnomad OTH

AF:

0.531

GnomAD3 exomes

AF:

0.614

AC:

153557

AN:

249928

Hom.:

49761

AF XY:

0.616

AC XY:

83179

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.706

Gnomad ASJ exome

AF:

0.438

Gnomad EAS exome

AF:

0.878

Gnomad SAS exome

AF:

0.653

Gnomad FIN exome

AF:

0.668

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.601

GnomAD4 exome

AF:

0.603

AC:

867434

AN:

1439658

Hom.:

267328

Cov.:

AF XY:

0.603

AC XY:

432945

AN XY:

717660

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.700

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.833

Gnomad4 SAS exome

AF:

0.645

Gnomad4 FIN exome

AF:

0.668

Gnomad4 NFE exome

AF:

0.602

Gnomad4 OTH exome

AF:

0.581

GnomAD4 genome

AF:

0.506

AC:

76820

AN:

151814

Hom.:

22328

Cov.:

AF XY:

0.516

AC XY:

38284

AN XY:

74198

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.627

Gnomad4 ASJ

AF:

0.445

Gnomad4 EAS

AF:

0.849

Gnomad4 SAS

AF:

0.670

Gnomad4 FIN

AF:

0.677

Gnomad4 NFE

AF:

0.598

Gnomad4 OTH

AF:

0.533

Alfa

AF:

0.469

Hom.:

2712

Bravo

AF:

0.492

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CHARGE syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.8

DANN

Benign

0.82

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over