chr15-47388210-A-C

Variant names:

• chr15-47388210-A-C
• rs281284
• ENST00000558014.5:c.-238-24183A>C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-238-24183A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 151,994 control chromosomes in the GnomAD database, including 8,855 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 0.28 (8855 hom., cov: 31)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.743
• 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

ENSG00000259221 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-238-24183A>C		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.-238-24183A>C		intron_variant	Intron 1 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-238-24183A>C		intron_variant	Intron 2 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-322-24183A>C		intron_variant	Intron 1 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42722 AN: 151876 Hom.: 8813 Cov.: 31

Gnomad AFR AF: 0.569

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.282 AC: 42835 AN: 151994 Hom.: 8855 Cov.: 31 AF XY: 0.279 AC XY: 20717 AN XY: 74298

African (AFR) AF: 0.569 AC: 23566 AN: 41396

American (AMR) AF: 0.239 AC: 3642 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 768 AN: 3464

East Asian (EAS) AF: 0.447 AC: 2303 AN: 5154

South Asian (SAS) AF: 0.262 AC: 1260 AN: 4818

European-Finnish (FIN) AF: 0.0930 AC: 986 AN: 10600

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9545 AN: 67986

Other (OTH) AF: 0.258 AC: 544 AN: 2110

Alfa AF: 0.228 Hom.: 807

Bravo AF: 0.305

Asia WGS AF: 0.425 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.87
DANN	Benign	0.51
PhyloP100		-0.74
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: rs281284; hg19: chr15-47680407;