rs3735514

chr7-84002201-T-Cchr7-84002201-T-G

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.1361-155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,082 control chromosomes in the GnomAD database, including 4,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4306 hom., cov: 33)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0760

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=-0.78).
• BP6: Variant 7-84002201-T-C is Benign according to our data. Variant chr7-84002201-T-C is described in ClinVar as [Benign]. Clinvar id is 1234621.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.1361-155A>G		intron_variant		ENST00000265362.9
SEMA3A	XM_005250110.4	c.1361-155A>G		intron_variant
SEMA3A	XM_047419751.1	c.1361-155A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-155A>G		intron_variant		1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.1361-155A>G		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35661 AN: 151964 Hom.: 4307 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.235 AC: 35670 AN: 152082 Hom.: 4306 Cov.: 33 AF XY: 0.238 AC XY: 17726 AN XY: 74346

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.226

Alfa AF: 0.238 Hom.: 564

Bravo AF: 0.226

Asia WGS AF: 0.233 AC: 811 AN: 3476

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	-0.78
Cadd	Benign	4.4
Dann	Benign	0.73

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: rs3735514; hg19: chr7-83631517; COSMIC: COSV54894059;