rs2245441

Variant names:

• chr7-83405438-T-A
• rs2245441
• NM_012431.3:c.998+12A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-83405438-T-A
• chr7-83405438-T-C
• chr7-83405438-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012431.3(SEMA3E):​c.998+12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 1,591,472 control chromosomes in the GnomAD database, including 289,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (22328 hom., cov: 31)
  • Exomes 𝑓: 0.60 (267328 hom.)
• Consequence: SEMA3E NM_012431.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.173
• Publications: 13 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-83405438-T-A is Benign according to our data. Variant chr7-83405438-T-A is described in ClinVar as Benign. ClinVar VariationId is 260257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	NM_012431.3	MANE Select	c.998+12A>T		intron	N/A	NP_036563.1
	SEMA3E	NM_001178129.2		c.818+12A>T		intron	N/A	NP_001171600.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3E	ENST00000643230.2	MANE Select	c.998+12A>T		intron	N/A	ENSP00000496491.1
	SEMA3E	ENST00000642232.1		c.998+12A>T		intron	N/A	ENSP00000494064.1
	SEMA3E	ENST00000643441.1		n.983+12A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76792 AN: 151696 Hom.: 22313 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.669

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.531

GnomAD2 exomes AF: 0.614 AC: 153557 AN: 249928 AF XY: 0.616

Gnomad AFR exome AF: 0.198

Gnomad AMR exome AF: 0.706

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.878

Gnomad FIN exome AF: 0.668

Gnomad NFE exome AF: 0.599

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.603 AC: 867434 AN: 1439658 Hom.: 267328 Cov.: 28 AF XY: 0.603 AC XY: 432945 AN XY: 717660

African (AFR) AF: 0.188 AC: 6210 AN: 33114

American (AMR) AF: 0.700 AC: 31182 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.441 AC: 11435 AN: 25956

East Asian (EAS) AF: 0.833 AC: 32922 AN: 39544

South Asian (SAS) AF: 0.645 AC: 55383 AN: 85800

European-Finnish (FIN) AF: 0.668 AC: 35589 AN: 53304

Middle Eastern (MID) AF: 0.483 AC: 2754 AN: 5706

European-Non Finnish (NFE) AF: 0.602 AC: 657395 AN: 1092158

Other (OTH) AF: 0.581 AC: 34564 AN: 59540

GnomAD4 genome AF: 0.506 AC: 76820 AN: 151814 Hom.: 22328 Cov.: 31 AF XY: 0.516 AC XY: 38284 AN XY: 74198

African (AFR) AF: 0.205 AC: 8516 AN: 41450

American (AMR) AF: 0.627 AC: 9529 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1540 AN: 3462

East Asian (EAS) AF: 0.849 AC: 4373 AN: 5152

South Asian (SAS) AF: 0.670 AC: 3222 AN: 4810

European-Finnish (FIN) AF: 0.677 AC: 7154 AN: 10566

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40597 AN: 67858

Other (OTH) AF: 0.533 AC: 1122 AN: 2106

Alfa AF: 0.469 Hom.: 2712

Bravo AF: 0.492

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	6.8
DANN	Benign	0.82
PhyloP100		-0.17
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: rs2245441; hg19: chr7-83034754; COSMIC: COSV57091364; COSMIC: COSV57091364;