ENST00000558014.5:c.-86-18551G>A

Variant names:

• chr15-47582314-G-A
• rs10519132
• ENST00000558014.5:c.-86-18551G>A

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-86-18551G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,162 control chromosomes in the GnomAD database, including 2,534 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 (2534 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• 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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-18551G>A		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.-86-18551G>A		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-18551G>A		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-18551G>A		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24561 AN: 152044 Hom.: 2541 Cov.: 32

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.291

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.161 AC: 24545 AN: 152162 Hom.: 2534 Cov.: 32 AF XY: 0.166 AC XY: 12376 AN XY: 74372

African (AFR) AF: 0.0398 AC: 1654 AN: 41538

American (AMR) AF: 0.115 AC: 1764 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 670 AN: 3468

East Asian (EAS) AF: 0.120 AC: 620 AN: 5180

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4816

European-Finnish (FIN) AF: 0.291 AC: 3082 AN: 10574

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14757 AN: 67972

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.202 Hom.: 1876

Bravo AF: 0.141

Asia WGS AF: 0.150 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.1
DANN	Benign	0.56
PhyloP100		0.30
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10519132; hg19: chr15-47874511;