7-83438154-T-G

Variant names:

• chr7-83438154-T-G
• rs2247219
• NM_012431.3:c.457-19671A>C

Variant summary

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

The NM_012431.3(SEMA3E):​c.457-19671A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 151,864 control chromosomes in the GnomAD database, including 40,790 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 0.72 (40790 hom., cov: 32)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.457-19671A>C		intron_variant	Intron 4 of 16	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.277-19671A>C		intron_variant	Intron 4 of 16		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.457-19671A>C		intron_variant	Intron 4 of 16		NM_012431.3	ENSP00000496491.1

Frequencies

GnomAD3 genomes AF: 0.724 AC: 109847 AN: 151746 Hom.: 40770 Cov.: 32

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.735

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.807

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.724 AC: 109908 AN: 151864 Hom.: 40790 Cov.: 32 AF XY: 0.730 AC XY: 54216 AN XY: 74218

African (AFR) AF: 0.560 AC: 23174 AN: 41416

American (AMR) AF: 0.808 AC: 12339 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.735 AC: 2550 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5156 AN: 5174

South Asian (SAS) AF: 0.808 AC: 3889 AN: 4816

European-Finnish (FIN) AF: 0.817 AC: 8614 AN: 10542

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51676 AN: 67874

Other (OTH) AF: 0.745 AC: 1570 AN: 2106

Alfa AF: 0.747 Hom.: 20768

Bravo AF: 0.718

Asia WGS AF: 0.889 AC: 3078 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.38
PhyloP100		0.0040
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: rs2247219; hg19: chr7-83067470;