rs421853

Variant names:

• chr15-47452134-G-A
• rs421853
• ENST00000558014.5:c.-158-18340G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47452134-G-A
• chr15-47452134-G-C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-158-18340G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 151,776 control chromosomes in the GnomAD database, including 47,201 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 (47201 hom., cov: 30)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.681
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-158-18340G>A		intron_variant	Intron 2 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-158-18340G>A		intron_variant	Intron 2 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-158-18340G>A		intron_variant	Intron 3 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-242-18340G>A		intron_variant	Intron 2 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.782 AC: 118603 AN: 151658 Hom.: 47149 Cov.: 30

Gnomad AFR AF: 0.899

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.796

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

GnomAD4 genome AF: 0.782 AC: 118712 AN: 151776 Hom.: 47201 Cov.: 30 AF XY: 0.784 AC XY: 58159 AN XY: 74136

African (AFR) AF: 0.899 AC: 37265 AN: 41448

American (AMR) AF: 0.835 AC: 12706 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2438 AN: 3468

East Asian (EAS) AF: 0.972 AC: 4988 AN: 5134

South Asian (SAS) AF: 0.801 AC: 3857 AN: 4814

European-Finnish (FIN) AF: 0.715 AC: 7530 AN: 10538

Middle Eastern (MID) AF: 0.738 AC: 217 AN: 294

European-Non Finnish (NFE) AF: 0.699 AC: 47423 AN: 67842

Other (OTH) AF: 0.792 AC: 1670 AN: 2108

Alfa AF: 0.735 Hom.: 68704

Bravo AF: 0.802

Asia WGS AF: 0.864 AC: 3004 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.57
PhyloP100		-0.68
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: rs421853; hg19: chr15-47744331;