rs4603502

Variant names:

• chr15-47582457-T-C
• rs4603502
• ENST00000558014.5:c.-86-18408T>C

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-86-18408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,148 control chromosomes in the GnomAD database, including 5,693 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 (5693 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 7 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=-0.65).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 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.-86-18408T>C		intron	N/A	NP_001185928.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-86-18408T>C		intron	N/A	ENSP00000452815.1
	SEMA6D	ENST00000559184.5	TSL:4	c.-86-18408T>C		intron	N/A	ENSP00000453097.1
	SEMA6D	ENST00000560636.5	TSL:4	c.-170-18408T>C		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38871 AN: 152030 Hom.: 5683 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.357

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.256 AC: 38892 AN: 152148 Hom.: 5693 Cov.: 32 AF XY: 0.254 AC XY: 18879 AN XY: 74350

African (AFR) AF: 0.122 AC: 5047 AN: 41520

American (AMR) AF: 0.357 AC: 5463 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3468

East Asian (EAS) AF: 0.461 AC: 2381 AN: 5164

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4820

European-Finnish (FIN) AF: 0.233 AC: 2463 AN: 10584

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.300 AC: 20415 AN: 67982

Other (OTH) AF: 0.298 AC: 631 AN: 2114

Alfa AF: 0.287 Hom.: 3630

Bravo AF: 0.264

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	8.6
DANN	Benign	0.77
PhyloP100		-0.073
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: rs4603502; hg19: chr15-47874654;