rs12914000

Variant names:

• chr15-47614521-T-C
• rs12914000
• ENST00000558014.5:c.-55+13625T>C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-55+13625T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,250 control chromosomes in the GnomAD database, including 1,317 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 0.11 (1317 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-55+13625T>C		intron_variant	Intron 4 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-55+13625T>C		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-55+13625T>C		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-55+11063T>C		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16737 AN: 152132 Hom.: 1317 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0700

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0712

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.0809

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

GnomAD4 genome AF: 0.110 AC: 16734 AN: 152250 Hom.: 1317 Cov.: 32 AF XY: 0.111 AC XY: 8225 AN XY: 74432

African (AFR) AF: 0.0284 AC: 1182 AN: 41576

American (AMR) AF: 0.0699 AC: 1069 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0719 AC: 346 AN: 4814

European-Finnish (FIN) AF: 0.197 AC: 2084 AN: 10598

Middle Eastern (MID) AF: 0.0685 AC: 20 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11357 AN: 67990

Other (OTH) AF: 0.0795 AC: 168 AN: 2112

Alfa AF: 0.153 Hom.: 1607

Bravo AF: 0.0945

Asia WGS AF: 0.0340 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		0.17
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: rs12914000; hg19: chr15-47906718;