rs1797225

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-87+6137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,040 control chromosomes in the GnomAD database, including 50,057 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 0.80 ( 50057 hom., cov: 31)

Consequence

SEMA6D
ENST00000558014.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.955
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=-0.94).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA6DNM_001198999.2 linkuse as main transcriptc.-87+6137G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA6DENST00000558014.5 linkuse as main transcriptc.-87+6137G>A intron_variant 1 A1Q8NFY4-2
SEMA6DENST00000559184.5 linkuse as main transcriptc.-87+6137G>A intron_variant 4
SEMA6DENST00000560636.5 linkuse as main transcriptc.-171+6137G>A intron_variant 4

Frequencies

GnomAD3 genomes
AF:
0.803
AC:
122038
AN:
151922
Hom.:
49992
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.946
Gnomad AMI
AF:
0.704
Gnomad AMR
AF:
0.839
Gnomad ASJ
AF:
0.704
Gnomad EAS
AF:
0.998
Gnomad SAS
AF:
0.871
Gnomad FIN
AF:
0.718
Gnomad MID
AF:
0.726
Gnomad NFE
AF:
0.709
Gnomad OTH
AF:
0.802
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.803
AC:
122162
AN:
152040
Hom.:
50057
Cov.:
31
AF XY:
0.805
AC XY:
59832
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.946
Gnomad4 AMR
AF:
0.839
Gnomad4 ASJ
AF:
0.704
Gnomad4 EAS
AF:
0.998
Gnomad4 SAS
AF:
0.870
Gnomad4 FIN
AF:
0.718
Gnomad4 NFE
AF:
0.709
Gnomad4 OTH
AF:
0.805
Alfa
AF:
0.740
Hom.:
21671
Bravo
AF:
0.821
Asia WGS
AF:
0.940
AC:
3266
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.94
CADD
Benign
0.52
DANN
Benign
0.62

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: rs1797225; hg19: chr15-47768879; API