chr15-47586845-G-A

Variant names:

• chr15-47586845-G-A
• rs12905212
• ENST00000558014.5:c.-86-14020G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000558014.5(SEMA6D):​c.-86-14020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000678 in 147,472 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000068 (0 hom., cov: 27)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460
• Publications: 3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-14020G>A		intron_variant	Intron 3 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-86-14020G>A		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-14020G>A		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-14020G>A		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.00000678 AC: 1 AN: 147472 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000678 AC: 1 AN: 147472 Hom.: 0 Cov.: 27 AF XY: 0.0000140 AC XY: 1 AN XY: 71430

African (AFR) AF: 0.00 AC: 0 AN: 39944

American (AMR) AF: 0.00 AC: 0 AN: 14924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00 AC: 0 AN: 5006

South Asian (SAS) AF: 0.00 AC: 0 AN: 4620

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67292

Other (OTH) AF: 0.00 AC: 0 AN: 2024

Alfa AF: 0.00 Hom.: 521

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	2.3
DANN	Benign	0.51
PhyloP100		0.046

Splicing

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

Other links and lift over

dbSNP: rs12905212; hg19: chr15-47879042;