7-83367515-A-T

Position:

• chr7-83367515-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012431.3(SEMA3E):​c.*71T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,464,550 control chromosomes in the GnomAD database, including 10,372 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.095 (827 hom., cov: 32)
  • Exomes 𝑓: 0.12 (9545 hom.)
• Consequence: SEMA3E NM_012431.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.637

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 7-83367515-A-T is Benign according to our data. Variant chr7-83367515-A-T is described in ClinVar as [Benign]. Clinvar id is 1291034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3E	NM_012431.3	c.*71T>A		3_prime_UTR_variant	17/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2	c.*71T>A		3_prime_UTR_variant	17/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2	c.*71T>A		3_prime_UTR_variant	17/17		NM_012431.3	ENSP00000496491	P1
SEMA3E	ENST00000643441.1	n.2384T>A		non_coding_transcript_exon_variant	17/17

Frequencies

GnomAD3 genomes AF: 0.0951 AC: 14141 AN: 148712 Hom.: 822 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0952

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.116 AC: 153011 AN: 1315724 Hom.: 9545 Cov.: 20 AF XY: 0.118 AC XY: 78471 AN XY: 662806

Gnomad4 AFR exome AF: 0.0217

Gnomad4 AMR exome AF: 0.154

Gnomad4 ASJ exome AF: 0.0973

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.0918

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.118

GnomAD4 genome AF: 0.0951 AC: 14146 AN: 148826 Hom.: 827 Cov.: 32 AF XY: 0.0976 AC XY: 7112 AN XY: 72842

Gnomad4 AFR AF: 0.0249

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0952

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.117

Alfa AF: 0.0937 Hom.: 92

Bravo AF: 0.0923

Asia WGS AF: 0.133 AC: 461 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.7
DANN	Benign	0.79

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: rs75164403; hg19: chr7-82996831;