rs6955597

chr7-84129031-C-Achr7-84129031-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_006080.3(SEMA3A):c.333+92G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 997,558 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.81

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 7-84129031-C-A is Benign according to our data. Variant chr7-84129031-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1208050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00658 (1001/152046) while in subpopulation AFR AF= 0.0207 (860/41480). AF 95% confidence interval is 0.0196. There are 13 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 994 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.333+92G>T		intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.333+92G>T		intron_variant
SEMA3A	XM_047419751.1	c.333+92G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.333+92G>T		intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000420047.1	c.333+92G>T		intron_variant		4
SEMA3A	ENST00000436949.5	c.333+92G>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.00654 AC: 994 AN: 151928 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0206

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00558

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000530

Gnomad OTH AF: 0.00383

GnomAD4 exome AF: 0.00119 AC: 1006 AN: 845512 Hom.: 4 AF XY: 0.00115 AC XY: 509 AN XY: 443902

Gnomad4 AFR exome AF: 0.0189

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000554

Gnomad4 SAS exome AF: 0.00235

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000354

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.00658 AC: 1001 AN: 152046 Hom.: 13 Cov.: 32 AF XY: 0.00623 AC XY: 463 AN XY: 74336

Gnomad4 AFR AF: 0.0207

Gnomad4 AMR AF: 0.00557

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000530

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.00741

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.054
Dann	Benign	0.16

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: rs6955597; hg19: chr7-83758347;