rs4775708

Variant names:

• chr15-47745452-C-A
• rs4775708
• NM_001358351.3:c.-54-14293C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47745452-C-A
• chr15-47745452-C-T

Variant summary

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

The NM_001358352.2(SEMA6D):​c.-54-14293C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,266 control chromosomes in the GnomAD database, including 3,771 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 0.21 (3771 hom., cov: 33)
• Consequence: SEMA6D NM_001358352.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 2 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358352.2. 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_001358351.3	MANE Select	c.-54-14293C>A		intron	N/A	NP_001345280.1
	SEMA6D	NM_001358352.2		c.-54-14293C>A		intron	N/A	NP_001345281.1
	SEMA6D	NM_153618.2		c.-54-14293C>A		intron	N/A	NP_705871.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.-54-14293C>A		intron	N/A	ENSP00000446152.3
	SEMA6D	ENST00000316364.9	TSL:1	c.-54-14293C>A		intron	N/A	ENSP00000324857.5
	SEMA6D	ENST00000354744.8	TSL:1	c.-54-14293C>A		intron	N/A	ENSP00000346786.4

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31494 AN: 152150 Hom.: 3773 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.207 AC: 31499 AN: 152266 Hom.: 3771 Cov.: 33 AF XY: 0.207 AC XY: 15435 AN XY: 74438

African (AFR) AF: 0.127 AC: 5275 AN: 41558

American (AMR) AF: 0.190 AC: 2906 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.00598 AC: 31 AN: 5184

South Asian (SAS) AF: 0.190 AC: 917 AN: 4824

European-Finnish (FIN) AF: 0.287 AC: 3044 AN: 10596

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17688 AN: 68016

Other (OTH) AF: 0.216 AC: 457 AN: 2114

Alfa AF: 0.159 Hom.: 513

Bravo AF: 0.190

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.046
DANN	Benign	0.49
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4775708; hg19: chr15-48037649;