rs586799

chr15-47732725-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001358351.3(SEMA6D):c.-55+15033A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,098 control chromosomes in the GnomAD database, including 7,940 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 0.29 (7940 hom., cov: 33)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001358351.3	c.-55+15033A>G		intron_variant		ENST00000536845.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000536845.7	c.-55+15033A>G		intron_variant		2	NM_001358351.3	P4

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44238 AN: 151982 Hom.: 7941 Cov.: 33

Gnomad AFR AF: 0.0774

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.291 AC: 44230 AN: 152098 Hom.: 7940 Cov.: 33 AF XY: 0.286 AC XY: 21273 AN XY: 74344

Gnomad4 AFR AF: 0.0771

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.286

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.314

Alfa AF: 0.366 Hom.: 4862

Bravo AF: 0.288

Asia WGS AF: 0.248 AC: 862 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	8.3
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs586799; hg19: chr15-48024922;