rs17374298

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000558014.5(SEMA6D):​c.-87+31736G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,146 control chromosomes in the GnomAD database, including 2,543 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2543 hom., cov: 32)

Consequence

SEMA6D
ENST00000558014.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

Publications

0 publications found
Variant links:
Genes affected
SEMA6D (HGNC:16770): (semaphorin 6D) Semaphorins are a large family, including both secreted and membrane associated proteins, many of which have been implicated as inhibitors or chemorepellents in axon pathfinding, fasciculation and branching, and target selection. All semaphorins possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Additional sequence motifs C-terminal to the semaphorin domain allow classification into distinct subfamilies. Results demonstrate that transmembrane semaphorins, like the secreted ones, can act as repulsive axon guidance cues. This gene encodes a class 6 vertebrate transmembrane semaphorin that demonstrates alternative splicing. Several transcript variants have been identified and expression of the distinct encoded isoforms is thought to be regulated in a tissue- and development-dependent manner. [provided by RefSeq, Nov 2010]
SEMA6D Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SEMA6DNM_001198999.2 linkc.-87+31736G>C intron_variant Intron 3 of 19 NP_001185928.1 Q8NFY4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SEMA6DENST00000558014.5 linkc.-87+31736G>C intron_variant Intron 3 of 19 1 ENSP00000452815.1 Q8NFY4-2
SEMA6DENST00000559184.5 linkc.-87+31736G>C intron_variant Intron 4 of 5 4 ENSP00000453097.1 H0YL82
SEMA6DENST00000560636.5 linkc.-171+31736G>C intron_variant Intron 3 of 5 4 ENSP00000453420.1

Frequencies

GnomAD3 genomes
AF:
0.160
AC:
24350
AN:
152028
Hom.:
2548
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0395
Gnomad AMI
AF:
0.239
Gnomad AMR
AF:
0.123
Gnomad ASJ
AF:
0.194
Gnomad EAS
AF:
0.0473
Gnomad SAS
AF:
0.276
Gnomad FIN
AF:
0.288
Gnomad MID
AF:
0.152
Gnomad NFE
AF:
0.220
Gnomad OTH
AF:
0.169
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.160
AC:
24336
AN:
152146
Hom.:
2543
Cov.:
32
AF XY:
0.165
AC XY:
12256
AN XY:
74366
show subpopulations
African (AFR)
AF:
0.0394
AC:
1636
AN:
41546
American (AMR)
AF:
0.123
AC:
1875
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.194
AC:
673
AN:
3468
East Asian (EAS)
AF:
0.0474
AC:
245
AN:
5166
South Asian (SAS)
AF:
0.276
AC:
1329
AN:
4820
European-Finnish (FIN)
AF:
0.288
AC:
3034
AN:
10546
Middle Eastern (MID)
AF:
0.143
AC:
42
AN:
294
European-Non Finnish (NFE)
AF:
0.220
AC:
14937
AN:
68000
Other (OTH)
AF:
0.165
AC:
347
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1007
2013
3020
4026
5033
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
284
568
852
1136
1420
<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:
0.180
Hom.:
389
Bravo
AF:
0.140
Asia WGS
AF:
0.129
AC:
450
AN:
3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Benign
0.67
PhyloP100
2.7
Mutation Taster
=100/0
polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs17374298; hg19: chr15-47794478; API