chr15-47568439-A-G

Variant names:

• chr15-47568439-A-G
• rs1435763
• ENST00000558014.5:c.-86-32426A>G

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-86-32426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 151,952 control chromosomes in the GnomAD database, including 39,744 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 0.72 (39744 hom., cov: 31)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.517
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-86-32426A>G		intron	N/A	NP_001185928.1	Q8NFY4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-86-32426A>G		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-86-32426A>G		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-170-32426A>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.721 AC: 109497 AN: 151834 Hom.: 39706 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.718

Gnomad OTH AF: 0.685

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

GnomAD4 genome AF: 0.721 AC: 109586 AN: 151952 Hom.: 39744 Cov.: 31 AF XY: 0.724 AC XY: 53732 AN XY: 74254

African (AFR) AF: 0.762 AC: 31572 AN: 41460

American (AMR) AF: 0.655 AC: 9993 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2340 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2718 AN: 5158

South Asian (SAS) AF: 0.776 AC: 3741 AN: 4818

European-Finnish (FIN) AF: 0.769 AC: 8097 AN: 10534

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.718 AC: 48768 AN: 67950

Other (OTH) AF: 0.686 AC: 1447 AN: 2108

Alfa AF: 0.673 Hom.: 2241

Bravo AF: 0.707

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.86
PhyloP100		0.52
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: rs1435763; hg19: chr15-47860636;