rs2371545

chr7-83367703-T-C

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.2211A>G(p.Arg737=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,936 control chromosomes in the GnomAD database, including 2,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (1250 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (1088 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.993

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-83367703-T-C is Benign according to our data. Variant chr7-83367703-T-C is described in ClinVar as [Benign]. Clinvar id is 416920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.993 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.2211A>G	p.Arg737=	synonymous_variant	17/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.2031A>G	p.Arg677=	synonymous_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.2211A>G	p.Arg737=	synonymous_variant	17/17		NM_012431.3	P1
SEMA3E	ENST00000643441.1	n.2196A>G		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10607 AN: 151938 Hom.: 1243 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0465

GnomAD3 exomes AF: 0.0190 AC: 4780 AN: 251490 Hom.: 493 AF XY: 0.0142 AC XY: 1927 AN XY: 135922

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000523

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00977

GnomAD4 exome AF: 0.00751 AC: 10975 AN: 1461880 Hom.: 1088 Cov.: 32 AF XY: 0.00664 AC XY: 4828 AN XY: 727242

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.000918

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000603

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000670

Gnomad4 OTH exome AF: 0.0171

GnomAD4 genome AF: 0.0700 AC: 10651 AN: 152056 Hom.: 1250 Cov.: 32 AF XY: 0.0677 AC XY: 5034 AN XY: 74344

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.0274

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0194 Hom.: 361

Bravo AF: 0.0807

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 23, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 22, 2018	- -

CHARGE syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	6.5
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs2371545; hg19: chr7-82997019;