Variant rs10234961 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.1361-28G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,302,130 control chromosomes in the GnomAD database, including 472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.035 ( 221 hom., cov: 33)

Exomes 𝑓: 0.013 ( 251 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.325

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-84002074-C-G is Benign according to our data. Variant chr7-84002074-C-G is described in ClinVar as [Benign]. Clinvar id is 1183281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SEMA3A	NM_006080.3 linkuse as main transcript	c.1361-28G>C	intron_variant	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4 linkuse as main transcript	c.1361-28G>C	intron_variant		XP_005250167.1
SEMA3A	XM_047419751.1 linkuse as main transcript	c.1361-28G>C	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.1361-28G>C		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.1361-28G>C		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes

AF:

0.0348

AC:

5295

AN:

152060

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0990

Gnomad AMI

AF:

0.00440

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.0510

Gnomad NFE

AF:

0.00943

Gnomad OTH

AF:

0.0311

GnomAD3 exomes

AF:

0.0171

AC:

4095

AN:

239940

Hom.:

AF XY:

0.0167

AC XY:

2177

AN XY:

130218

show subpopulations

Gnomad AFR exome

AF:

0.0991

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.0171

Gnomad SAS exome

AF:

0.0209

Gnomad FIN exome

AF:

0.00123

Gnomad NFE exome

AF:

0.00958

Gnomad OTH exome

AF:

0.0151

GnomAD4 exome

AF:

0.0128

AC:

14696

AN:

1149950

Hom.:

251

Cov.:

AF XY:

0.0129

AC XY:

7561

AN XY:

587198

show subpopulations

Gnomad4 AFR exome

AF:

0.102

Gnomad4 AMR exome

AF:

0.0113

Gnomad4 ASJ exome

AF:

0.0131

Gnomad4 EAS exome

AF:

0.0138

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.00153

Gnomad4 NFE exome

AF:

0.00919

Gnomad4 OTH exome

AF:

0.0193

GnomAD4 genome

AF:

0.0349

AC:

5312

AN:

152180

Hom.:

221

Cov.:

AF XY:

0.0337

AC XY:

2507

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0991

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.0188

Gnomad4 SAS

AF:

0.0209

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00943

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0229

Hom.:

Bravo

AF:

0.0381

Asia WGS

AF:

0.0210

AC:

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	GeneDx	Aug 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.0

DANN

Benign

0.62

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

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