chr15-47450146-G-T

Variant names:

• chr15-47450146-G-T
• rs1496917
• ENST00000558014.5:c.-158-20328G>T

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-158-20328G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 152,028 control chromosomes in the GnomAD database, including 6,153 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 0.26 (6153 hom., cov: 33)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198999.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-158-20328G>T		intron	N/A	NP_001185928.1	Q8NFY4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-158-20328G>T		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-158-20328G>T		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-242-20328G>T		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39008 AN: 151910 Hom.: 6148 Cov.: 33

Gnomad AFR AF: 0.0787

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.257 AC: 39011 AN: 152028 Hom.: 6153 Cov.: 33 AF XY: 0.259 AC XY: 19203 AN XY: 74286

African (AFR) AF: 0.0785 AC: 3260 AN: 41514

American (AMR) AF: 0.376 AC: 5743 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 1067 AN: 3472

East Asian (EAS) AF: 0.511 AC: 2631 AN: 5146

South Asian (SAS) AF: 0.261 AC: 1254 AN: 4812

European-Finnish (FIN) AF: 0.289 AC: 3051 AN: 10556

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.310 AC: 21076 AN: 67956

Other (OTH) AF: 0.304 AC: 641 AN: 2108

Alfa AF: 0.128 Hom.: 454

Bravo AF: 0.262

Asia WGS AF: 0.319 AC: 1108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		0.34
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: rs1496917; hg19: chr15-47742343;