15-47584946-A-T

Variant names:

• chr15-47584946-A-T
• rs1435735
• ENST00000558014.5:c.-86-15919A>T

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-86-15919A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,062 control chromosomes in the GnomAD database, including 16,169 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 0.46 (16169 hom., cov: 33)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.447
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-86-15919A>T		intron	N/A	NP_001185928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-86-15919A>T		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-86-15919A>T		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-170-15919A>T		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69152 AN: 151944 Hom.: 16156 Cov.: 33

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.490

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

GnomAD4 genome AF: 0.455 AC: 69197 AN: 152062 Hom.: 16169 Cov.: 33 AF XY: 0.452 AC XY: 33581 AN XY: 74326

African (AFR) AF: 0.468 AC: 19403 AN: 41456

American (AMR) AF: 0.572 AC: 8735 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1602 AN: 3468

East Asian (EAS) AF: 0.668 AC: 3452 AN: 5170

South Asian (SAS) AF: 0.381 AC: 1835 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3558 AN: 10586

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29141 AN: 67970

Other (OTH) AF: 0.488 AC: 1030 AN: 2112

Alfa AF: 0.428 Hom.: 1744

Bravo AF: 0.481

Asia WGS AF: 0.484 AC: 1680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.41
DANN	Benign	0.54
PhyloP100		-0.45
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: rs1435735; hg19: chr15-47877143;