7-83527891-C-T

Variant names:

• chr7-83527891-C-T
• rs2535368
• NM_012431.3:c.116-37617G>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.116-37617G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 151,452 control chromosomes in the GnomAD database, including 1,983 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 0.16 (1983 hom., cov: 32)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0880
• Publications: 5 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):

• CHD7-related CHARGE syndrome

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia
• CHARGE syndrome

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• Kallmann syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012431.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	NM_012431.3	MANE Select	c.116-37617G>A		intron	N/A	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.-65-37617G>A		intron	N/A	NP_001171600.1	O15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	ENST00000643230.2	MANE Select	c.116-37617G>A		intron	N/A	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000891111.1		c.116-37617G>A		intron	N/A	ENSP00000561170.1
	SEMA3E	ENST00000642232.1		c.116-37617G>A		intron	N/A	ENSP00000494064.1	A0A2R8YCX5

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24494 AN: 151334 Hom.: 1979 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.162 AC: 24521 AN: 151452 Hom.: 1983 Cov.: 32 AF XY: 0.161 AC XY: 11872 AN XY: 73968

African (AFR) AF: 0.193 AC: 7974 AN: 41304

American (AMR) AF: 0.132 AC: 2003 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3464

East Asian (EAS) AF: 0.212 AC: 1093 AN: 5144

South Asian (SAS) AF: 0.108 AC: 517 AN: 4790

European-Finnish (FIN) AF: 0.125 AC: 1297 AN: 10410

Middle Eastern (MID) AF: 0.143 AC: 41 AN: 286

European-Non Finnish (NFE) AF: 0.153 AC: 10353 AN: 67850

Other (OTH) AF: 0.167 AC: 350 AN: 2100

Alfa AF: 0.152 Hom.: 917

Bravo AF: 0.162

Asia WGS AF: 0.179 AC: 617 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		0.088
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: rs2535368; hg19: chr7-83157207;