chr15-47532886-T-C

Variant names:

• chr15-47532886-T-C
• rs16959669
• ENST00000558014.5:c.-87+62341T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558014.5(SEMA6D):​c.-87+62341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,164 control chromosomes in the GnomAD database, including 2,104 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 0.13 (2104 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-87+62341T>C		intron_variant	Intron 3 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-87+62341T>C		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-87+62341T>C		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-171+62341T>C		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19154 AN: 152046 Hom.: 2101 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.0125

Gnomad SAS AF: 0.0731

Gnomad FIN AF: 0.0363

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.115

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.126 AC: 19179 AN: 152164 Hom.: 2104 Cov.: 32 AF XY: 0.122 AC XY: 9041 AN XY: 74398

African (AFR) AF: 0.297 AC: 12318 AN: 41464

American (AMR) AF: 0.0829 AC: 1267 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3466

East Asian (EAS) AF: 0.0123 AC: 64 AN: 5184

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4822

European-Finnish (FIN) AF: 0.0363 AC: 385 AN: 10604

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4253 AN: 68024

Other (OTH) AF: 0.114 AC: 241 AN: 2116

Alfa AF: 0.0807 Hom.: 3046

Bravo AF: 0.138

Asia WGS AF: 0.0610 AC: 211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.54
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs16959669; hg19: chr15-47825083;