15-47501797-C-G

Variant names:

• chr15-47501797-C-G
• rs1656602
• ENST00000558014.5:c.-87+31252C>G

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-87+31252C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,042 control chromosomes in the GnomAD database, including 47,366 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 0.78 (47366 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.933 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001198999.2. 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.-87+31252C>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.-87+31252C>G		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+31252C>G		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+31252C>G		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118549 AN: 151924 Hom.: 47314 Cov.: 32

Gnomad AFR AF: 0.941

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.811

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.683

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.780 AC: 118657 AN: 152042 Hom.: 47366 Cov.: 32 AF XY: 0.782 AC XY: 58140 AN XY: 74320

African (AFR) AF: 0.941 AC: 39080 AN: 41544

American (AMR) AF: 0.801 AC: 12231 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2361 AN: 3472

East Asian (EAS) AF: 0.927 AC: 4797 AN: 5174

South Asian (SAS) AF: 0.810 AC: 3900 AN: 4816

European-Finnish (FIN) AF: 0.705 AC: 7404 AN: 10502

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.683 AC: 46432 AN: 67952

Other (OTH) AF: 0.775 AC: 1639 AN: 2114

Alfa AF: 0.703 Hom.: 4506

Bravo AF: 0.797

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.19
DANN	Benign	0.61
PhyloP100		-1.0
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: rs1656602; hg19: chr15-47793994;