7-84002098-A-T

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.1361-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 984,588 control chromosomes in the GnomAD database, including 30,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4423 hom., cov: 33)

Exomes 𝑓: 0.25 ( 26476 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.328

Publications

5 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, SD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
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

new If you want to explore the variant's impact on the transcript NM_006080.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.9).

BP6

Variant 7-84002098-A-T is Benign according to our data. Variant chr7-84002098-A-T is described in ClinVar as Benign. ClinVar VariationId is 1231850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	NM_006080.3	MANE Select	c.1361-52T>A		intron	N/A	NP_006071.1	Q14563

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.1361-52T>A	intron	N/A	ENSP00000265362.3	Q14563
SEMA3A	ENST00000436949.5	TSL:5	c.1361-52T>A	intron	N/A	ENSP00000415260.1	Q14563
SEMA3A	ENST00000864988.1		c.1361-52T>A	intron	N/A	ENSP00000535047.1

Frequencies

GnomAD3 genomes

AF:

0.238

AC:

36115

AN:

151976

Hom.:

4424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.300

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.231

GnomAD2 exomes

AF:

0.241

AC:

51086

AN:

212320

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.248

Gnomad AMR exome

AF:

0.178

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.307

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.251

AC:

209220

AN:

832492

Hom.:

26476

Cov.:

AF XY:

0.254

AC XY:

111104

AN XY:

437968

show subpopulations

African (AFR)

AF:

0.261

AC:

5260

AN:

20148

American (AMR)

AF:

0.185

AC:

6445

AN:

34916

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

5134

AN:

20370

East Asian (EAS)

AF:

0.172

AC:

6106

AN:

35498

South Asian (SAS)

AF:

0.329

AC:

22228

AN:

67548

European-Finnish (FIN)

AF:

0.304

AC:

15578

AN:

51302

Middle Eastern (MID)

AF:

0.335

AC:

1490

AN:

4446

European-Non Finnish (NFE)

AF:

0.245

AC:

137247

AN:

559274

Other (OTH)

AF:

0.250

AC:

9732

AN:

38990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

7617

15234

22850

30467

38084

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3278

6556

9834

13112

16390

<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:

0.238

AC:

36126

AN:

152096

Hom.:

4423

Cov.:

AF XY:

0.241

AC XY:

17921

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.249

AC:

10340

AN:

41500

American (AMR)

AF:

0.203

AC:

3103

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

869

AN:

3472

East Asian (EAS)

AF:

0.162

AC:

833

AN:

5154

South Asian (SAS)

AF:

0.314

AC:

1512

AN:

4814

European-Finnish (FIN)

AF:

0.300

AC:

3168

AN:

10572

Middle Eastern (MID)

AF:

0.296

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15504

AN:

67986

Other (OTH)

AF:

0.230

AC:

486

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1432

2864

4295

5727

7159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.178

Hom.:

544

Bravo

AF:

0.229

Asia WGS

AF:

0.234

AC:

816

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

(source)

DANN

Benign

0.69

PhyloP100

-0.33

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over