rs11070582

Positions:

• chr15-47394393-C-T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-238-18000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 151,992 control chromosomes in the GnomAD database, including 4,408 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 0.22 (4408 hom., cov: 33)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499

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]

(HGNC:):

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 (EAS) 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_001198999.2	c.-238-18000C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000559799.5	n.510+1168G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33074 AN: 151874 Hom.: 4394 Cov.: 33

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.218 AC: 33140 AN: 151992 Hom.: 4408 Cov.: 33 AF XY: 0.216 AC XY: 16043 AN XY: 74286

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.217

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.102

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.218

Alfa AF: 0.160 Hom.: 3270

Bravo AF: 0.236

Asia WGS AF: 0.382 AC: 1327 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	11
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11070582; hg19: chr15-47686590;