7-83367540-T-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.*46A>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 0.0114 in 1,591,280 control chromosomes in the GnomAD database, including 1,716 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (905 hom., cov: 32)
  • Exomes 𝑓: 0.0062 (811 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0650

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=-0.91).
• BP6: Variant 7-83367540-T-G is Benign according to our data. Variant chr7-83367540-T-G is described in ClinVar as [Benign]. Clinvar id is 1174248.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.*46A>C		3_prime_UTR_variant	17/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.*46A>C		3_prime_UTR_variant	17/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*46A>C		3_prime_UTR_variant	17/17		NM_012431.3	P1
SEMA3E	ENST00000643441.1	n.2359A>C		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.0601 AC: 9133 AN: 152054 Hom.: 904 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0420

GnomAD3 exomes AF: 0.0159 AC: 3982 AN: 250610 Hom.: 364 AF XY: 0.0118 AC XY: 1599 AN XY: 135678

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000425

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000529

Gnomad OTH exome AF: 0.00687

GnomAD4 exome AF: 0.00620 AC: 8928 AN: 1439108 Hom.: 811 Cov.: 27 AF XY: 0.00543 AC XY: 3896 AN XY: 717448

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000479

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000361

Gnomad4 OTH exome AF: 0.0139

GnomAD4 genome AF: 0.0602 AC: 9164 AN: 152172 Hom.: 905 Cov.: 32 AF XY: 0.0577 AC XY: 4297 AN XY: 74426

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000897

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0238 Hom.: 75

Bravo AF: 0.0694

Asia WGS AF: 0.00982 AC: 35 AN: 3478

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	-0.91
Cadd	Benign	0.24
Dann	Benign	0.32

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: rs4473980; hg19: chr7-82996856;