rs2722974

Positions:

• chr7-83400122-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012431.3(SEMA3E):​c.1272G>A​(p.Leu424Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 1,613,362 control chromosomes in the GnomAD database, including 159,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (11704 hom., cov: 31)
  • Exomes 𝑓: 0.45 (148046 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.06

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 7-83400122-C-T is Benign according to our data. Variant chr7-83400122-C-T is described in ClinVar as [Benign]. Clinvar id is 260254.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83400122-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.06 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.1272G>A	p.Leu424Leu	synonymous_variant	11/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.1092G>A	p.Leu364Leu	synonymous_variant	11/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.1272G>A	p.Leu424Leu	synonymous_variant	11/17		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000642232.1	c.1272G>A	p.Leu424Leu	synonymous_variant	11/17			ENSP00000494064.1
SEMA3E	ENST00000643441.1	n.1257G>A		non_coding_transcript_exon_variant	11/17

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54754 AN: 151726 Hom.: 11688 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.374

GnomAD3 exomes AF: 0.425 AC: 106757 AN: 251224 Hom.: 23790 AF XY: 0.430 AC XY: 58331 AN XY: 135776

Gnomad AFR exome AF: 0.112

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.462

Gnomad SAS exome AF: 0.455

Gnomad FIN exome AF: 0.494

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.432

GnomAD4 exome AF: 0.446 AC: 651188 AN: 1461518 Hom.: 148046 Cov.: 45 AF XY: 0.446 AC XY: 323995 AN XY: 727086

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.421

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.450

Gnomad4 SAS exome AF: 0.453

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.361 AC: 54779 AN: 151844 Hom.: 11704 Cov.: 31 AF XY: 0.366 AC XY: 27174 AN XY: 74174

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.410

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.378

Alfa AF: 0.399 Hom.: 7155

Bravo AF: 0.340

Asia WGS AF: 0.469 AC: 1630 AN: 3476

EpiCase AF: 0.446

EpiControl AF: 0.439

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

CHARGE syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.3
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs2722974; hg19: chr7-83029438; COSMIC: COSV57083429;