chr7-83466611-GA-G

Variant names:

• chr7-83466611-GA-G
• rs536827692
• NM_012431.3:c.337-11delT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_012431.3(SEMA3E):​c.337-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,609,948 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (2 hom.)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.07
• Publications: 0 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.

• BP6: Variant 7-83466611-GA-G is Benign according to our data. Variant chr7-83466611-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 235213.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 217 AD,Unknown gene.

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.337-11delT		intron	N/A	NP_036563.1	O15041-1
	SEMA3E	NM_001178129.2		c.157-11delT		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.337-11delT		intron	N/A	ENSP00000496491.1	O15041-1
	SEMA3E	ENST00000891111.1		c.337-11delT		intron	N/A	ENSP00000561170.1
	SEMA3E	ENST00000642232.1		c.337-11delT		intron	N/A	ENSP00000494064.1	A0A2R8YCX5

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 151728 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000387

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000984

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00143

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00246

Gnomad OTH AF: 0.000958

GnomAD2 exomes AF: 0.00138 AC: 342 AN: 247458 AF XY: 0.00148

Gnomad AFR exome AF: 0.000371

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00184

Gnomad NFE exome AF: 0.00217

Gnomad OTH exome AF: 0.000993

GnomAD4 exome AF: 0.00196 AC: 2852 AN: 1458102 Hom.: 2 Cov.: 31 AF XY: 0.00190 AC XY: 1376 AN XY: 725498

African (AFR) AF: 0.000451 AC: 15 AN: 33282

American (AMR) AF: 0.00104 AC: 46 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26062

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.000790 AC: 68 AN: 86028

European-Finnish (FIN) AF: 0.00151 AC: 78 AN: 51530

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5750

European-Non Finnish (NFE) AF: 0.00229 AC: 2544 AN: 1111248

Other (OTH) AF: 0.00166 AC: 100 AN: 60244

GnomAD4 genome AF: 0.00143 AC: 217 AN: 151846 Hom.: 1 Cov.: 32 AF XY: 0.00138 AC XY: 102 AN XY: 74178

African (AFR) AF: 0.000386 AC: 16 AN: 41478

American (AMR) AF: 0.000983 AC: 15 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4804

European-Finnish (FIN) AF: 0.00143 AC: 15 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 67874

Other (OTH) AF: 0.000948 AC: 2 AN: 2110

Alfa AF: 0.00131 Hom.: 0

Bravo AF: 0.00127

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	CHARGE syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism

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: rs536827692; hg19: chr7-83095927; COSMIC: COSV57079867; COSMIC: COSV57079867;