chr15-47671757-C-T

Variant names:

• chr15-47671757-C-T
• rs10519138
• ENST00000558014.5:c.-55+70861C>T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-55+70861C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 151,740 control chromosomes in the GnomAD database, including 3,089 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 0.18 (3089 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 3 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=-0.71).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-55+70861C>T		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+70861C>T		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-55+70861C>T		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-55+68299C>T		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27713 AN: 151622 Hom.: 3089 Cov.: 32

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.183 AC: 27712 AN: 151740 Hom.: 3089 Cov.: 32 AF XY: 0.187 AC XY: 13879 AN XY: 74128

African (AFR) AF: 0.0480 AC: 1984 AN: 41368

American (AMR) AF: 0.173 AC: 2641 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.133 AC: 684 AN: 5154

South Asian (SAS) AF: 0.268 AC: 1284 AN: 4796

European-Finnish (FIN) AF: 0.310 AC: 3247 AN: 10478

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16331 AN: 67920

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.225 Hom.: 2181

Bravo AF: 0.164

Asia WGS AF: 0.165 AC: 578 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.2
DANN	Benign	0.63
PhyloP100		0.36
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: rs10519138; hg19: chr15-47963954;