ENST00000558014.5:c.-87+6137G>A

Variant names:

• chr15-47476682-G-A
• rs1797225
• ENST00000558014.5:c.-87+6137G>A

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-87+6137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,040 control chromosomes in the GnomAD database, including 50,057 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 0.80 (50057 hom., cov: 31)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.955
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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+6137G>A		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+6137G>A		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+6137G>A		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+6137G>A		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122038 AN: 151922 Hom.: 49992 Cov.: 31

Gnomad AFR AF: 0.946

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.704

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.726

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.802

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

GnomAD4 genome AF: 0.803 AC: 122162 AN: 152040 Hom.: 50057 Cov.: 31 AF XY: 0.805 AC XY: 59832 AN XY: 74280

African (AFR) AF: 0.946 AC: 39276 AN: 41524

American (AMR) AF: 0.839 AC: 12793 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 2439 AN: 3466

East Asian (EAS) AF: 0.998 AC: 5149 AN: 5158

South Asian (SAS) AF: 0.870 AC: 4191 AN: 4816

European-Finnish (FIN) AF: 0.718 AC: 7570 AN: 10550

Middle Eastern (MID) AF: 0.733 AC: 214 AN: 292

European-Non Finnish (NFE) AF: 0.709 AC: 48189 AN: 67972

Other (OTH) AF: 0.805 AC: 1700 AN: 2112

Alfa AF: 0.738 Hom.: 23672

Bravo AF: 0.821

Asia WGS AF: 0.940 AC: 3266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.52
DANN	Benign	0.62
PhyloP100		-0.95
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: rs1797225; hg19: chr15-47768879;