ENST00000558014.5:c.-86-14441G>T

Variant names:

• chr15-47586424-G-T
• rs1865648
• ENST00000558014.5:c.-86-14441G>T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-86-14441G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,996 control chromosomes in the GnomAD database, including 5,748 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 0.26 (5748 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-14441G>T		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.-86-14441G>T		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-14441G>T		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-14441G>T		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39202 AN: 151874 Hom.: 5738 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.258 AC: 39221 AN: 151996 Hom.: 5748 Cov.: 32 AF XY: 0.257 AC XY: 19074 AN XY: 74306

African (AFR) AF: 0.130 AC: 5390 AN: 41456

American (AMR) AF: 0.363 AC: 5544 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1169 AN: 3462

East Asian (EAS) AF: 0.460 AC: 2369 AN: 5154

South Asian (SAS) AF: 0.226 AC: 1089 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2457 AN: 10550

Middle Eastern (MID) AF: 0.411 AC: 120 AN: 292

European-Non Finnish (NFE) AF: 0.299 AC: 20313 AN: 67970

Other (OTH) AF: 0.301 AC: 636 AN: 2112

Alfa AF: 0.275 Hom.: 4513

Bravo AF: 0.267

Asia WGS AF: 0.284 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.72
PhyloP100		0.11
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: rs1865648; hg19: chr15-47878621;