7-83484896-C-T

Variant names:

• chr7-83484896-C-T
• rs2713189
• NM_012431.3:c.276+5218G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012431.3(SEMA3E):​c.276+5218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 151,910 control chromosomes in the GnomAD database, including 14,742 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 0.42 (14742 hom., cov: 32)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 3 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.276+5218G>A		intron_variant	Intron 2 of 16	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.96+5218G>A		intron_variant	Intron 2 of 16		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.276+5218G>A		intron_variant	Intron 2 of 16		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000642232.1	c.276+5218G>A		intron_variant	Intron 2 of 16			ENSP00000494064.1
SEMA3E	ENST00000442159.3	n.232+5218G>A		intron_variant	Intron 2 of 5	5
SEMA3E	ENST00000643441.1	n.261+5218G>A		intron_variant	Intron 2 of 16

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64112 AN: 151792 Hom.: 14725 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.422 AC: 64151 AN: 151910 Hom.: 14742 Cov.: 32 AF XY: 0.433 AC XY: 32127 AN XY: 74228

African (AFR) AF: 0.245 AC: 10158 AN: 41422

American (AMR) AF: 0.467 AC: 7113 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1231 AN: 3466

East Asian (EAS) AF: 0.630 AC: 3247 AN: 5156

South Asian (SAS) AF: 0.601 AC: 2890 AN: 4806

European-Finnish (FIN) AF: 0.568 AC: 5986 AN: 10546

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.470 AC: 31918 AN: 67960

Other (OTH) AF: 0.445 AC: 939 AN: 2112

Alfa AF: 0.302 Hom.: 899

Bravo AF: 0.406

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.63
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2713189; hg19: chr7-83114212;