rs7809708

chr7-83963175-T-C

Variant summary

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

The NM_006080.3(SEMA3A):c.1860+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,606,842 control chromosomes in the GnomAD database, including 54,156 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5528 hom., cov: 32)
  • Exomes 𝑓: 0.25 (48628 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.162

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=-0.79).
• BP6: Variant 7-83963175-T-C is Benign according to our data. Variant chr7-83963175-T-C is described in ClinVar as [Benign]. Clinvar id is 1292758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.1860+30A>G		intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.1860+30A>G		intron_variant
SEMA3A	XM_047419751.1	c.1860+30A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1860+30A>G		intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.1860+30A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40120 AN: 152000 Hom.: 5527 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.0424

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.289

GnomAD3 exomes AF: 0.225 AC: 56125 AN: 249096 Hom.: 7105 AF XY: 0.227 AC XY: 30629 AN XY: 134870

Gnomad AFR exome AF: 0.316

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.228

Gnomad EAS exome AF: 0.0452

Gnomad SAS exome AF: 0.172

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.271

Gnomad OTH exome AF: 0.247

GnomAD4 exome AF: 0.253 AC: 367587 AN: 1454724 Hom.: 48628 Cov.: 30 AF XY: 0.252 AC XY: 182512 AN XY: 724116

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.159

Gnomad4 ASJ exome AF: 0.225

Gnomad4 EAS exome AF: 0.0312

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.262

Gnomad4 NFE exome AF: 0.268

Gnomad4 OTH exome AF: 0.249

GnomAD4 genome AF: 0.264 AC: 40142 AN: 152118 Hom.: 5528 Cov.: 32 AF XY: 0.261 AC XY: 19401 AN XY: 74358

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.0427

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.288

Alfa AF: 0.263 Hom.: 1045

Bravo AF: 0.263

Asia WGS AF: 0.137 AC: 479 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

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.4
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7809708; hg19: chr7-83592491; COSMIC: COSV54864733;