chr7-84002201-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006080.3(SEMA3A):​c.1361-155A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 152,082 control chromosomes in the GnomAD database, including 4,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4306 hom., cov: 33)

Consequence

SEMA3A
NM_006080.3 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0760

Publications

2 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 7-84002201-T-C is Benign according to our data. Variant chr7-84002201-T-C is described in ClinVar as Benign. ClinVar VariationId is 1234621.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA3ANM_006080.3 linkc.1361-155A>G intron_variant Intron 11 of 16 ENST00000265362.9 NP_006071.1 Q14563
SEMA3AXM_005250110.4 linkc.1361-155A>G intron_variant Intron 14 of 19 XP_005250167.1 Q14563
SEMA3AXM_047419751.1 linkc.1361-155A>G intron_variant Intron 15 of 20 XP_047275707.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA3AENST00000265362.9 linkc.1361-155A>G intron_variant Intron 11 of 16 1 NM_006080.3 ENSP00000265362.3 Q14563
SEMA3AENST00000436949.5 linkc.1361-155A>G intron_variant Intron 12 of 17 5 ENSP00000415260.1 Q14563

Frequencies

GnomAD3 genomes
AF:
0.235
AC:
35661
AN:
151964
Hom.:
4307
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.239
Gnomad AMI
AF:
0.248
Gnomad AMR
AF:
0.202
Gnomad ASJ
AF:
0.250
Gnomad EAS
AF:
0.162
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.301
Gnomad MID
AF:
0.307
Gnomad NFE
AF:
0.228
Gnomad OTH
AF:
0.227
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.235
AC:
35670
AN:
152082
Hom.:
4306
Cov.:
33
AF XY:
0.238
AC XY:
17726
AN XY:
74346
show subpopulations
African (AFR)
AF:
0.239
AC:
9902
AN:
41484
American (AMR)
AF:
0.202
AC:
3082
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.250
AC:
868
AN:
3468
East Asian (EAS)
AF:
0.162
AC:
839
AN:
5176
South Asian (SAS)
AF:
0.314
AC:
1513
AN:
4822
European-Finnish (FIN)
AF:
0.301
AC:
3172
AN:
10550
Middle Eastern (MID)
AF:
0.296
AC:
87
AN:
294
European-Non Finnish (NFE)
AF:
0.228
AC:
15503
AN:
67996
Other (OTH)
AF:
0.226
AC:
478
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.499
Heterozygous variant carriers
0
1403
2806
4208
5611
7014
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
384
768
1152
1536
1920
<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:
0.228
Hom.:
5601
Bravo
AF:
0.226
Asia WGS
AF:
0.233
AC:
811
AN:
3476

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Aug 09, 2018
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
4.4
DANN
Benign
0.73
PhyloP100
-0.076
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs3735514; hg19: chr7-83631517; COSMIC: COSV54894059; API