7-83367330-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012431.3(SEMA3E):c.*256T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0274 in 406,682 control chromosomes in the GnomAD database, including 1,088 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (929 hom., cov: 32)
  • Exomes 𝑓: 0.0075 (159 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0480

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-83367330-A-G is Benign according to our data. Variant chr7-83367330-A-G is described in ClinVar as [Benign]. Clinvar id is 1242507.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.*256T>C		3_prime_UTR_variant	17/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.*256T>C		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*256T>C		3_prime_UTR_variant	17/17		NM_012431.3	P1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9186 AN: 152134 Hom.: 928 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0421

GnomAD4 exome AF: 0.00750 AC: 1909 AN: 254430 Hom.: 159 Cov.: 3 AF XY: 0.00630 AC XY: 843 AN XY: 133914

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0136

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000508

Gnomad4 FIN exome AF: 0.0000753

Gnomad4 NFE exome AF: 0.000376

Gnomad4 OTH exome AF: 0.0159

GnomAD4 genome AF: 0.0605 AC: 9217 AN: 152252 Hom.: 929 Cov.: 32 AF XY: 0.0580 AC XY: 4320 AN XY: 74456

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0120 Hom.: 135

Bravo AF: 0.0694

Asia WGS AF: 0.00985 AC: 35 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.6
Dann	Benign	0.53

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

Publications

LitVar

Other links and lift over

dbSNP: rs10237682; hg19: chr7-82996646;