rs649483

Variant names:

• chr15-47349702-A-G
• rs649483
• ENST00000558014.5:c.-238-62691A>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The ENST00000558014.5(SEMA6D):​c.-238-62691A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,090 control chromosomes in the GnomAD database, including 19,714 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 0.47 (19714 hom., cov: 33)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-238-62691A>G		intron_variant	Intron 1 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-238-62691A>G		intron_variant	Intron 1 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-238-62691A>G		intron_variant	Intron 2 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-323+10483A>G		intron_variant	Intron 1 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71064 AN: 151972 Hom.: 19731 Cov.: 33

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.669

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.497

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

GnomAD4 genome AF: 0.467 AC: 71040 AN: 152090 Hom.: 19714 Cov.: 33 AF XY: 0.475 AC XY: 35338 AN XY: 74346

African (AFR) AF: 0.150 AC: 6247 AN: 41510

American (AMR) AF: 0.515 AC: 7863 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1990 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2305 AN: 5160

South Asian (SAS) AF: 0.610 AC: 2941 AN: 4824

European-Finnish (FIN) AF: 0.669 AC: 7073 AN: 10576

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40995 AN: 67966

Other (OTH) AF: 0.490 AC: 1034 AN: 2112

Alfa AF: 0.529 Hom.: 3126

Bravo AF: 0.440

Asia WGS AF: 0.452 AC: 1573 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Benign	19
DANN	Benign	0.84
PhyloP100		1.7
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: rs649483; hg19: chr15-47641899;