rs3801583

Variant names:

• chr7-83645868-C-T
• rs3801583
• NM_012431.3:c.115+2560G>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.115+2560G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 151,984 control chromosomes in the GnomAD database, including 398 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 0.057 (398 hom., cov: 31)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 1 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.115+2560G>A		intron_variant	Intron 1 of 16	ENST00000643230.2	NP_036563.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.115+2560G>A		intron_variant	Intron 1 of 16		NM_012431.3	ENSP00000496491.1
SEMA3E	ENST00000642232.1	c.115+2560G>A		intron_variant	Intron 1 of 16			ENSP00000494064.1
SEMA3E	ENST00000453333.2	n.115+2560G>A		intron_variant	Intron 1 of 2	3		ENSP00000415184.1

Frequencies

GnomAD3 genomes AF: 0.0565 AC: 8585 AN: 151866 Hom.: 396 Cov.: 31

Gnomad AFR AF: 0.0125

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0669

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

GnomAD4 genome AF: 0.0566 AC: 8601 AN: 151984 Hom.: 398 Cov.: 31 AF XY: 0.0590 AC XY: 4383 AN XY: 74298

African (AFR) AF: 0.0125 AC: 517 AN: 41518

American (AMR) AF: 0.108 AC: 1649 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 412 AN: 3462

East Asian (EAS) AF: 0.199 AC: 1025 AN: 5158

South Asian (SAS) AF: 0.0823 AC: 397 AN: 4822

European-Finnish (FIN) AF: 0.0541 AC: 572 AN: 10574

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0543 AC: 3683 AN: 67882

Other (OTH) AF: 0.0691 AC: 146 AN: 2114

Alfa AF: 0.0555 Hom.: 38

Bravo AF: 0.0588

Asia WGS AF: 0.135 AC: 470 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.40
DANN	Benign	0.41
PhyloP100		-1.2
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: rs3801583; hg19: chr7-83275184;