chr15-47516157-G-A

Variant names:

• chr15-47516157-G-A
• rs2059474
• ENST00000558014.5:c.-87+45612G>A

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+45612G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,968 control chromosomes in the GnomAD database, including 5,673 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 0.26 (5673 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001198999.2		c.-87+45612G>A		intron	N/A	NP_001185928.1	Q8NFY4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-87+45612G>A		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-87+45612G>A		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-171+45612G>A		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39529 AN: 151850 Hom.: 5666 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.260 AC: 39542 AN: 151968 Hom.: 5673 Cov.: 32 AF XY: 0.259 AC XY: 19262 AN XY: 74288

African (AFR) AF: 0.152 AC: 6313 AN: 41464

American (AMR) AF: 0.339 AC: 5181 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.325 AC: 1126 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2435 AN: 5130

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4820

European-Finnish (FIN) AF: 0.268 AC: 2834 AN: 10556

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.290 AC: 19710 AN: 67948

Other (OTH) AF: 0.303 AC: 639 AN: 2112

Alfa AF: 0.256 Hom.: 707

Bravo AF: 0.269

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.52
DANN	Benign	0.71
PhyloP100		-0.26
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: rs2059474; hg19: chr15-47808354;