ENST00000558014.5:c.-87+32514A>G

Variant names:

• chr15-47503059-A-G
• rs16959595
• ENST00000558014.5:c.-87+32514A>G

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-87+32514A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0918 in 152,214 control chromosomes in the GnomAD database, including 937 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 0.092 (937 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 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+32514A>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.-87+32514A>G		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+32514A>G		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+32514A>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13959 AN: 152096 Hom.: 935 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0980

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

GnomAD4 genome AF: 0.0918 AC: 13975 AN: 152214 Hom.: 937 Cov.: 32 AF XY: 0.0938 AC XY: 6983 AN XY: 74426

African (AFR) AF: 0.0996 AC: 4134 AN: 41522

American (AMR) AF: 0.173 AC: 2643 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3472

East Asian (EAS) AF: 0.323 AC: 1668 AN: 5168

South Asian (SAS) AF: 0.0898 AC: 433 AN: 4820

European-Finnish (FIN) AF: 0.0344 AC: 365 AN: 10610

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0621 AC: 4225 AN: 68006

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.0761 Hom.: 735

Bravo AF: 0.106

Asia WGS AF: 0.199 AC: 689 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		-0.086
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: rs16959595; hg19: chr15-47795256;