15-47617316-A-G

Variant names:

• chr15-47617316-A-G
• rs938043
• ENST00000558014.5:c.-55+16420A>G

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-55+16420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,134 control chromosomes in the GnomAD database, including 5,456 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 0.25 (5456 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.98
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-55+16420A>G		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+16420A>G		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-55+16420A>G		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-55+13858A>G		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37492 AN: 152018 Hom.: 5445 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.247 AC: 37507 AN: 152134 Hom.: 5456 Cov.: 32 AF XY: 0.246 AC XY: 18316 AN XY: 74346

African (AFR) AF: 0.103 AC: 4268 AN: 41536

American (AMR) AF: 0.344 AC: 5261 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1192 AN: 3472

East Asian (EAS) AF: 0.460 AC: 2370 AN: 5156

South Asian (SAS) AF: 0.225 AC: 1082 AN: 4818

European-Finnish (FIN) AF: 0.246 AC: 2607 AN: 10580

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19869 AN: 67976

Other (OTH) AF: 0.290 AC: 612 AN: 2108

Alfa AF: 0.230 Hom.: 726

Bravo AF: 0.253

Asia WGS AF: 0.280 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.34
DANN	Benign	0.39
PhyloP100		-2.0
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: rs938043; hg19: chr15-47909513;