ENST00000558014.5:c.-86-64736C>A

Variant names:

• chr15-47536129-C-A
• rs1035704
• ENST00000558014.5:c.-86-64736C>A

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-86-64736C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.785 in 152,102 control chromosomes in the GnomAD database, including 47,831 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 (47831 hom., cov: 31)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-64736C>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.-86-64736C>A		intron_variant	Intron 3 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-64736C>A		intron_variant	Intron 4 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-64736C>A		intron_variant	Intron 3 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.785 AC: 119232 AN: 151984 Hom.: 47776 Cov.: 31

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.799

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.785 AC: 119344 AN: 152102 Hom.: 47831 Cov.: 31 AF XY: 0.786 AC XY: 58426 AN XY: 74334

African (AFR) AF: 0.944 AC: 39185 AN: 41528

American (AMR) AF: 0.799 AC: 12208 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2394 AN: 3472

East Asian (EAS) AF: 0.888 AC: 4581 AN: 5158

South Asian (SAS) AF: 0.817 AC: 3941 AN: 4826

European-Finnish (FIN) AF: 0.710 AC: 7502 AN: 10564

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 47056 AN: 67960

Other (OTH) AF: 0.779 AC: 1643 AN: 2110

Alfa AF: 0.718 Hom.: 23300

Bravo AF: 0.801

Asia WGS AF: 0.825 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.36
DANN	Benign	0.77
PhyloP100		-1.9
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: rs1035704; hg19: chr15-47828326;