ENST00000558014.5:c.-87+57689T>C

Variant names:

• chr15-47528234-T-C
• rs890153
• ENST00000558014.5:c.-87+57689T>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+57689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.507 in 152,062 control chromosomes in the GnomAD database, including 21,111 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 0.51 (21111 hom., cov: 33)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.985
• Publications: 5 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558014.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-87+57689T>C		intron	N/A	NP_001185928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-87+57689T>C		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+57689T>C		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+57689T>C		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 77027 AN: 151944 Hom.: 21069 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.327

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.507 AC: 77126 AN: 152062 Hom.: 21111 Cov.: 33 AF XY: 0.501 AC XY: 37235 AN XY: 74328

African (AFR) AF: 0.729 AC: 30259 AN: 41482

American (AMR) AF: 0.500 AC: 7638 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2771 AN: 5176

South Asian (SAS) AF: 0.399 AC: 1921 AN: 4816

European-Finnish (FIN) AF: 0.353 AC: 3724 AN: 10564

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.409 AC: 27825 AN: 67966

Other (OTH) AF: 0.510 AC: 1076 AN: 2108

Alfa AF: 0.451 Hom.: 42735

Bravo AF: 0.532

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		-0.98
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: rs890153; hg19: chr15-47820431;