15-47586845-G-C

Variant names:

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

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-86-14020G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 147,322 control chromosomes in the GnomAD database, including 14,431 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 0.44 (14431 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-14020G>C		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>C		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-14020G>C		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-14020G>C		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.438 AC: 64512 AN: 147260 Hom.: 14420 Cov.: 27

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.317

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.523

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.438 AC: 64546 AN: 147322 Hom.: 14431 Cov.: 27 AF XY: 0.438 AC XY: 31259 AN XY: 71384

African (AFR) AF: 0.390 AC: 15591 AN: 39934

American (AMR) AF: 0.568 AC: 8479 AN: 14918

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1605 AN: 3448

East Asian (EAS) AF: 0.673 AC: 3355 AN: 4982

South Asian (SAS) AF: 0.397 AC: 1830 AN: 4612

European-Finnish (FIN) AF: 0.358 AC: 3219 AN: 8992

Middle Eastern (MID) AF: 0.535 AC: 153 AN: 286

European-Non Finnish (NFE) AF: 0.432 AC: 29060 AN: 67228

Other (OTH) AF: 0.479 AC: 969 AN: 2024

Alfa AF: 0.249 Hom.: 521

Bravo AF: 0.454

Asia WGS AF: 0.480 AC: 1663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	1.8
DANN	Benign	0.49
PhyloP100		0.046
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: rs12905212; hg19: chr15-47879042;