7-83367390-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012431.3(SEMA3E):c.*196T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 595,034 control chromosomes in the GnomAD database, including 3,207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.094 (717 hom., cov: 32)
  • Exomes 𝑓: 0.10 (2490 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.100

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-83367390-A-T is Benign according to our data. Variant chr7-83367390-A-T is described in ClinVar as [Benign]. Clinvar id is 1233803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.*196T>A		3_prime_UTR_variant	17/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.*196T>A		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*196T>A		3_prime_UTR_variant	17/17		NM_012431.3	P1

Frequencies

GnomAD3 genomes AF: 0.0943 AC: 14350 AN: 152098 Hom.: 720 Cov.: 32

Gnomad AFR AF: 0.0762

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0688

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.116

GnomAD4 exome AF: 0.102 AC: 45270 AN: 442818 Hom.: 2490 Cov.: 5 AF XY: 0.102 AC XY: 23802 AN XY: 233762

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.0869

Gnomad4 FIN exome AF: 0.0727

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.0943 AC: 14353 AN: 152216 Hom.: 717 Cov.: 32 AF XY: 0.0952 AC XY: 7085 AN XY: 74424

Gnomad4 AFR AF: 0.0761

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.175

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0841

Gnomad4 FIN AF: 0.0688

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0934 Hom.: 87

Bravo AF: 0.0965

Asia WGS AF: 0.0940 AC: 325 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.022
Dann	Benign	0.47

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: rs3801661; hg19: chr7-82996706;