rs2722963

chr7-83428712-G-Achr7-83428712-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012431.3(SEMA3E):c.457-10229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 151,974 control chromosomes in the GnomAD database, including 33,337 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 0.64 (33337 hom., cov: 32)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.457-10229C>T		intron_variant		ENST00000643230.2
SEMA3E	NM_001178129.2	c.277-10229C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.457-10229C>T		intron_variant			NM_012431.3	P1

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96816 AN: 151856 Hom.: 33323 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.752

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.734

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.637 AC: 96864 AN: 151974 Hom.: 33337 Cov.: 32 AF XY: 0.648 AC XY: 48133 AN XY: 74302

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.663

Alfa AF: 0.676 Hom.: 6283

Bravo AF: 0.624

Asia WGS AF: 0.846 AC: 2931 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	4.0
Dann	Benign	0.75

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: rs2722963; hg19: chr7-83058028;