ENST00000558014.5:c.-239+104324T>C

Variant names:

• chr15-47288742-T-C
• rs766132
• ENST00000558014.5:c.-239+104324T>C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-239+104324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,006 control chromosomes in the GnomAD database, including 23,318 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 0.55 (23318 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.593 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.-239+104324T>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.-239+104324T>C		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-239+47372T>C		intron	N/A	ENSP00000453097.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83391 AN: 151888 Hom.: 23299 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.549 AC: 83464 AN: 152006 Hom.: 23318 Cov.: 32 AF XY: 0.548 AC XY: 40718 AN XY: 74298

African (AFR) AF: 0.499 AC: 20696 AN: 41438

American (AMR) AF: 0.534 AC: 8153 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2030 AN: 3466

East Asian (EAS) AF: 0.306 AC: 1579 AN: 5160

South Asian (SAS) AF: 0.518 AC: 2496 AN: 4814

European-Finnish (FIN) AF: 0.564 AC: 5956 AN: 10558

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.598 AC: 40654 AN: 67990

Other (OTH) AF: 0.544 AC: 1143 AN: 2102

Alfa AF: 0.573 Hom.: 97129

Bravo AF: 0.544

Asia WGS AF: 0.407 AC: 1414 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.57
DANN	Benign	0.40
PhyloP100		-0.24
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: rs766132; hg19: chr15-47580939;