ENST00000558014.5:c.-54-51180T>C

Variant names:

• chr15-47708565-T-C
• rs1224660
• ENST00000558014.5:c.-54-51180T>C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-54-51180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,282 control chromosomes in the GnomAD database, including 63,529 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 0.91 (63529 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558014.5. 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.-54-51180T>C		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.-54-51180T>C		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-54-51180T>C		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-54-51180T>C		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138346 AN: 152164 Hom.: 63490 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.909 AC: 138445 AN: 152282 Hom.: 63529 Cov.: 32 AF XY: 0.904 AC XY: 67326 AN XY: 74456

African (AFR) AF: 0.906 AC: 37646 AN: 41558

American (AMR) AF: 0.860 AC: 13161 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.962 AC: 3341 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2562 AN: 5172

South Asian (SAS) AF: 0.839 AC: 4042 AN: 4820

European-Finnish (FIN) AF: 0.942 AC: 9996 AN: 10606

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.951 AC: 64683 AN: 68038

Other (OTH) AF: 0.904 AC: 1912 AN: 2114

Alfa AF: 0.937 Hom.: 51609

Bravo AF: 0.899

Asia WGS AF: 0.672 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.41
PhyloP100		-1.1
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: rs1224660; hg19: chr15-48000762;