rs16959719

Variant names:

• chr15-47591756-A-G
• rs16959719
• ENST00000558014.5:c.-86-9109A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-47591756-A-G
• chr15-47591756-A-T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-86-9109A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 152,296 control chromosomes in the GnomAD database, including 494 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 0.064 (494 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133
• 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

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 = 0.182 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.-86-9109A>G		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.-86-9109A>G		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-86-9109A>G		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-170-9109A>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.0645 AC: 9820 AN: 152178 Hom.: 492 Cov.: 32

Gnomad AFR AF: 0.0165

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0678

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0850

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0672

Gnomad OTH AF: 0.0732

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

GnomAD4 genome AF: 0.0645 AC: 9820 AN: 152296 Hom.: 494 Cov.: 32 AF XY: 0.0673 AC XY: 5008 AN XY: 74466

African (AFR) AF: 0.0165 AC: 685 AN: 41580

American (AMR) AF: 0.128 AC: 1951 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0678 AC: 235 AN: 3468

East Asian (EAS) AF: 0.192 AC: 995 AN: 5184

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4822

European-Finnish (FIN) AF: 0.0672 AC: 713 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0672 AC: 4569 AN: 68022

Other (OTH) AF: 0.0739 AC: 156 AN: 2112

Alfa AF: 0.0279 Hom.: 31

Bravo AF: 0.0692

Asia WGS AF: 0.142 AC: 491 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	1.3
DANN	Benign	0.39
PhyloP100		-0.13
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: rs16959719; hg19: chr15-47883953;