rs12914000

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001198999.2(SEMA6D):​c.-55+13625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,250 control chromosomes in the GnomAD database, including 1,317 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 0.11 ( 1317 hom., cov: 32)

Consequence

SEMA6D
NM_001198999.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.172
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SEMA6DNM_001198999.2 linkuse as main transcriptc.-55+13625T>C intron_variant NP_001185928.1 Q8NFY4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SEMA6DENST00000558014.5 linkuse as main transcriptc.-55+13625T>C intron_variant 1 ENSP00000452815.1 Q8NFY4-2
SEMA6DENST00000559184.5 linkuse as main transcriptc.-55+13625T>C intron_variant 4 ENSP00000453097.1 H0YL82
SEMA6DENST00000560636.5 linkuse as main transcriptc.-55+11063T>C intron_variant 4 ENSP00000453420.1

Frequencies

GnomAD3 genomes
AF:
0.110
AC:
16737
AN:
152132
Hom.:
1317
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0285
Gnomad AMI
AF:
0.0779
Gnomad AMR
AF:
0.0700
Gnomad ASJ
AF:
0.125
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.0712
Gnomad FIN
AF:
0.197
Gnomad MID
AF:
0.0732
Gnomad NFE
AF:
0.167
Gnomad OTH
AF:
0.0809
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.110
AC:
16734
AN:
152250
Hom.:
1317
Cov.:
32
AF XY:
0.111
AC XY:
8225
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0284
Gnomad4 AMR
AF:
0.0699
Gnomad4 ASJ
AF:
0.125
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.0719
Gnomad4 FIN
AF:
0.197
Gnomad4 NFE
AF:
0.167
Gnomad4 OTH
AF:
0.0795
Alfa
AF:
0.150
Hom.:
1098
Bravo
AF:
0.0945
Asia WGS
AF:
0.0340
AC:
122
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
3.2
DANN
Benign
0.52

Splicing

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.

Other links and lift over

dbSNP: rs12914000; hg19: chr15-47906718; API