rs3809485

Positions:

• chr15-47759259-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.-54-486A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 151,980 control chromosomes in the GnomAD database, including 18,766 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 0.49 (18766 hom., cov: 32)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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=-0.65).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001358351.3	c.-54-486A>G		intron_variant		ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7	c.-54-486A>G		intron_variant		2	NM_001358351.3	ENSP00000446152	P4

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74652 AN: 151862 Hom.: 18752 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.492 AC: 74714 AN: 151980 Hom.: 18766 Cov.: 32 AF XY: 0.497 AC XY: 36929 AN XY: 74266

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.422

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.481

Alfa AF: 0.507 Hom.: 5880

Bravo AF: 0.464

Asia WGS AF: 0.459 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.76

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: rs3809485; hg19: chr15-48051456;