rs2272221

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1174858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.668-20C>T	intron_variant	Intron 6 of 16	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.668-20C>T	intron_variant	Intron 9 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.668-20C>T	intron_variant	Intron 10 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.668-20C>T		intron_variant	Intron 6 of 16	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.668-20C>T		intron_variant	Intron 7 of 17	5		ENSP00000415260.1		Q14563

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

GnomAD2 exomes

AF:

0.366

AC:

89518

AN:

244800

AF XY:

0.364

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 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

African (AFR)

AF:

0.697

AC:

21933

AN:

31462

American (AMR)

AF:

0.340

AC:

14991

AN:

44108

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8541

AN:

25744

East Asian (EAS)

AF:

0.390

AC:

15312

AN:

39280

South Asian (SAS)

AF:

0.457

AC:

38613

AN:

84484

European-Finnish (FIN)

AF:

0.354

AC:

17785

AN:

50196

Middle Eastern (MID)

AF:

0.396

AC:

2240

AN:

5660

European-Non Finnish (NFE)

AF:

0.299

AC:

319766

AN:

1069908

Other (OTH)

AF:

0.348

AC:

20386

AN:

58616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

12268

24537

36805

49074

61342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10444

20888

31332

41776

52220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.432

AC:

65395

AN:

151522

Hom.:

16120

Cov.:

AF XY:

0.433

AC XY:

32023

AN XY:

74022

show subpopulations

African (AFR)

AF:

0.692

AC:

28520

AN:

41224

American (AMR)

AF:

0.362

AC:

5516

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1198

AN:

3466

East Asian (EAS)

AF:

0.364

AC:

1868

AN:

5138

South Asian (SAS)

AF:

0.454

AC:

2183

AN:

4804

European-Finnish (FIN)

AF:

0.343

AC:

3594

AN:

10466

Middle Eastern (MID)

AF:

0.367

AC:

108

AN:

294

European-Non Finnish (NFE)

AF:

0.314

AC:

21312

AN:

67876

Other (OTH)

AF:

0.395

AC:

833

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1697

3394

5091

6788

8485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.8

(source)

DANN

Benign

0.63

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over