Variant rs2272221 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.668-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,560,980 control chromosomes in the GnomAD database, including 95,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 16120 hom., cov: 32)

Exomes 𝑓: 0.33 ( 79324 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.188

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=-0.85).

BP6

Variant 7-84014371-G-A is Benign according to our data. Variant chr7-84014371-G-A is described in ClinVar as [Benign]. Clinvar id is 1174858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-84014371-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SEMA3A	NM_006080.3 linkuse as main transcript	c.668-20C>T	intron_variant	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4 linkuse as main transcript	c.668-20C>T	intron_variant		XP_005250167.1
SEMA3A	XM_047419751.1 linkuse as main transcript	c.668-20C>T	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.668-20C>T		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000436949.5 linkuse as main transcript	c.668-20C>T		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65317

AN:

151406

Hom.:

16094

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.363

Gnomad SAS

AF:

0.454

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.314

Gnomad OTH

AF:

0.395

GnomAD3 exomes

AF:

0.366

AC:

89518

AN:

244800

Hom.:

17328

AF XY:

0.364

AC XY:

48298

AN XY:

132606

show subpopulations

Gnomad AFR exome

AF:

0.695

Gnomad AMR exome

AF:

0.336

Gnomad ASJ exome

AF:

0.330

Gnomad EAS exome

AF:

0.343

Gnomad SAS exome

AF:

0.462

Gnomad FIN exome

AF:

0.352

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.346

GnomAD4 exome

AF:

0.326

AC:

459567

AN:

1409458

Hom.:

79324

Cov.:

AF XY:

0.329

AC XY:

231716

AN XY:

703954

show subpopulations

Gnomad4 AFR exome

AF:

0.697

Gnomad4 AMR exome

AF:

0.340

Gnomad4 ASJ exome

AF:

0.332

Gnomad4 EAS exome

AF:

0.390

Gnomad4 SAS exome

AF:

0.457

Gnomad4 FIN exome

AF:

0.354

Gnomad4 NFE exome

AF:

0.299

Gnomad4 OTH exome

AF:

0.348

GnomAD4 genome

AF:

0.432

AC:

65395

AN:

151522

Hom.:

16120

Cov.:

AF XY:

0.433

AC XY:

32023

AN XY:

74022

show subpopulations

Gnomad4 AFR

AF:

0.692

Gnomad4 AMR

AF:

0.362

Gnomad4 ASJ

AF:

0.346

Gnomad4 EAS

AF:

0.364

Gnomad4 SAS

AF:

0.454

Gnomad4 FIN

AF:

0.343

Gnomad4 NFE

AF:

0.314

Gnomad4 OTH

AF:

0.395

Alfa

AF:

0.370

Hom.:

2134

Bravo

AF:

0.443

Asia WGS

AF:

0.440

AC:

1531

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

DANN

Benign

0.63

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

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