ENST00000558014.5:c.-158-20737C>G

Variant names:

• chr15-47449737-C-G
• rs10519119
• ENST00000558014.5:c.-158-20737C>G

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-158-20737C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,942 control chromosomes in the GnomAD database, including 3,900 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 (3900 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.152
• 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=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-158-20737C>G		intron_variant	Intron 2 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-158-20737C>G		intron_variant	Intron 2 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-158-20737C>G		intron_variant	Intron 3 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-242-20737C>G		intron_variant	Intron 2 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31311 AN: 151824 Hom.: 3889 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.206 AC: 31364 AN: 151942 Hom.: 3900 Cov.: 32 AF XY: 0.205 AC XY: 15211 AN XY: 74264

African (AFR) AF: 0.333 AC: 13799 AN: 41420

American (AMR) AF: 0.222 AC: 3385 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 538 AN: 3468

East Asian (EAS) AF: 0.247 AC: 1271 AN: 5144

South Asian (SAS) AF: 0.157 AC: 756 AN: 4820

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10564

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9732 AN: 67960

Other (OTH) AF: 0.204 AC: 430 AN: 2106

Alfa AF: 0.166 Hom.: 315

Bravo AF: 0.222

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.56
PhyloP100		0.15
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: rs10519119; hg19: chr15-47741934;