chr7-83367703-T-C

Variant names:

• chr7-83367703-T-C
• rs2371545
• NM_012431.3:c.2211A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012431.3(SEMA3E):​c.2211A>G​(p.Arg737Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,936 control chromosomes in the GnomAD database, including 2,338 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (1250 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (1088 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.993
• 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):

• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 7-83367703-T-C is Benign according to our data. Variant chr7-83367703-T-C is described in ClinVar as Benign. ClinVar VariationId is 416920.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.993 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 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.2211A>G	p.Arg737Arg	synonymous	Exon 17 of 17	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.2031A>G	p.Arg677Arg	synonymous	Exon 17 of 17	NP_001171600.1	O15041-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	ENST00000643230.2	MANE Select	c.2211A>G	p.Arg737Arg	synonymous	Exon 17 of 17	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000891111.1		c.2205A>G	p.Arg735Arg	synonymous	Exon 17 of 17	ENSP00000561170.1
	SEMA3E	ENST00000643441.1		n.2196A>G		non_coding_transcript_exon	Exon 17 of 17

Frequencies

GnomAD3 genomes AF: 0.0698 AC: 10607 AN: 151938 Hom.: 1243 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0275

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0465

GnomAD2 exomes AF: 0.0190 AC: 4780 AN: 251490 AF XY: 0.0142

Gnomad AFR exome AF: 0.253

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00105

Gnomad OTH exome AF: 0.00977

GnomAD4 exome AF: 0.00751 AC: 10975 AN: 1461880 Hom.: 1088 Cov.: 32 AF XY: 0.00664 AC XY: 4828 AN XY: 727242

African (AFR) AF: 0.250 AC: 8355 AN: 33480

American (AMR) AF: 0.0153 AC: 683 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000918 AC: 24 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.000603 AC: 52 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.0140 AC: 81 AN: 5768

European-Non Finnish (NFE) AF: 0.000670 AC: 745 AN: 1112002

Other (OTH) AF: 0.0171 AC: 1033 AN: 60394

GnomAD4 genome AF: 0.0700 AC: 10651 AN: 152056 Hom.: 1250 Cov.: 32 AF XY: 0.0677 AC XY: 5034 AN XY: 74344

African (AFR) AF: 0.242 AC: 10039 AN: 41408

American (AMR) AF: 0.0274 AC: 419 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00131 AC: 89 AN: 68002

Other (OTH) AF: 0.0460 AC: 97 AN: 2110

Alfa AF: 0.0268 Hom.: 660

Bravo AF: 0.0807

Asia WGS AF: 0.0140 AC: 49 AN: 3478

EpiCase AF: 0.000981

EpiControl AF: 0.00172

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	CHARGE syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.5
DANN	Benign	0.62
PhyloP100		0.99
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: rs2371545; hg19: chr7-82997019;