rs628501

Variant names:

• chr15-47735131-C-G
• rs628501
• NM_001358351.3:c.-55+17439C>G

Variant summary

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

The NM_001358351.3(SEMA6D):​c.-55+17439C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 152,036 control chromosomes in the GnomAD database, including 4,196 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 0.22 (4196 hom., cov: 32)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.120
• 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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3	c.-55+17439C>G		intron_variant	Intron 1 of 18	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7	c.-55+17439C>G		intron_variant	Intron 1 of 18	2	NM_001358351.3	ENSP00000446152.3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33410 AN: 151916 Hom.: 4197 Cov.: 32

Gnomad AFR AF: 0.0897

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.220 AC: 33412 AN: 152036 Hom.: 4196 Cov.: 32 AF XY: 0.225 AC XY: 16713 AN XY: 74302

African (AFR) AF: 0.0895 AC: 3716 AN: 41508

American (AMR) AF: 0.248 AC: 3779 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1072 AN: 5168

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4814

European-Finnish (FIN) AF: 0.313 AC: 3297 AN: 10546

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.269 AC: 18276 AN: 67970

Other (OTH) AF: 0.228 AC: 481 AN: 2112

Alfa AF: 0.226 Hom.: 490

Bravo AF: 0.209

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs628501; hg19: chr15-48027328;