Variant rs3735513 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006080.3(SEMA3A):c.1361-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,509,330 control chromosomes in the GnomAD database, including 42,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4460 hom., cov: 33)

Exomes 𝑓: 0.24 ( 38394 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.51

Variant links:

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]

SEMA3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-84002060-T-C is Benign according to our data. Variant chr7-84002060-T-C is described in ClinVar as [Benign]. Clinvar id is 1601502.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-84002060-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
SEMA3A	NM_006080.3 linkuse as main transcript	c.1361-14A>G	intron_variant	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 linkuse as main transcript	c.1361-14A>G	intron_variant		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 linkuse as main transcript	c.1361-14A>G	intron_variant		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 linkuse as main transcript	c.1361-14A>G		intron_variant		1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.1361-14A>G		intron_variant		5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.239

AC:

36236

AN:

151930

Hom.:

4461

Cov.:

show subpopulations

Gnomad AFR

AF:

0.250

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.302

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.229

Gnomad OTH

AF:

0.231

GnomAD3 exomes

AF:

0.237

AC:

58101

AN:

244654

Hom.:

7271

AF XY:

0.245

AC XY:

32532

AN XY:

132620

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.241

Gnomad EAS exome

AF:

0.151

Gnomad SAS exome

AF:

0.321

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.241

GnomAD4 exome

AF:

0.236

AC:

320433

AN:

1357282

Hom.:

38394

Cov.:

AF XY:

0.239

AC XY:

162659

AN XY:

681322

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.175

Gnomad4 ASJ exome

AF:

0.246

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.321

Gnomad4 FIN exome

AF:

0.303

Gnomad4 NFE exome

AF:

0.229

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

AF:

0.238

AC:

36249

AN:

152048

Hom.:

4460

Cov.:

AF XY:

0.242

AC XY:

17988

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.250

Gnomad4 AMR

AF:

0.203

Gnomad4 ASJ

AF:

0.250

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.314

Gnomad4 FIN

AF:

0.302

Gnomad4 NFE

AF:

0.229

Gnomad4 OTH

AF:

0.230

Alfa

AF:

0.239

Hom.:

2739

Bravo

AF:

0.230

Asia WGS

AF:

0.237

AC:

827

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.31

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over