rs1369637

Variant names:

• chr15-47652630-A-G
• rs1369637
• ENST00000558014.5:c.-55+51734A>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+51734A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,196 control chromosomes in the GnomAD database, including 49,037 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 0.80 (49037 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.884
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000558014.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-55+51734A>G		intron	N/A	NP_001185928.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-55+51734A>G		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-55+51734A>G		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-55+49172A>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121760 AN: 152078 Hom.: 48986 Cov.: 32

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.823

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.801 AC: 121869 AN: 152196 Hom.: 49037 Cov.: 32 AF XY: 0.797 AC XY: 59301 AN XY: 74390

African (AFR) AF: 0.882 AC: 36655 AN: 41550

American (AMR) AF: 0.823 AC: 12589 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2687 AN: 3470

East Asian (EAS) AF: 0.864 AC: 4462 AN: 5166

South Asian (SAS) AF: 0.730 AC: 3521 AN: 4820

European-Finnish (FIN) AF: 0.695 AC: 7359 AN: 10588

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.765 AC: 52046 AN: 67994

Other (OTH) AF: 0.797 AC: 1683 AN: 2112

Alfa AF: 0.780 Hom.: 59091

Bravo AF: 0.816

Asia WGS AF: 0.835 AC: 2900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.44
DANN	Benign	0.58
PhyloP100		-0.88
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: rs1369637; hg19: chr15-47944827;