15-47513815-T-C

Variant names:

• chr15-47513815-T-C
• rs1610098
• ENST00000558014.5:c.-87+43270T>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+43270T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.465 in 152,096 control chromosomes in the GnomAD database, including 17,920 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 (17920 hom., cov: 33)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.831 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+43270T>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+43270T>C		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+43270T>C		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+43270T>C		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70596 AN: 151978 Hom.: 17880 Cov.: 33

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.851

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.465 AC: 70695 AN: 152096 Hom.: 17920 Cov.: 33 AF XY: 0.464 AC XY: 34475 AN XY: 74334

African (AFR) AF: 0.603 AC: 25016 AN: 41504

American (AMR) AF: 0.566 AC: 8645 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1325 AN: 3470

East Asian (EAS) AF: 0.852 AC: 4403 AN: 5170

South Asian (SAS) AF: 0.381 AC: 1838 AN: 4822

European-Finnish (FIN) AF: 0.318 AC: 3365 AN: 10570

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24738 AN: 67970

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.384 Hom.: 5131

Bravo AF: 0.496

Asia WGS AF: 0.598 AC: 2079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.87
DANN	Benign	0.31
PhyloP100		-0.82
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: rs1610098; hg19: chr15-47806012;