rs11634811

Variant names:

• chr15-47703539-G-A
• rs11634811
• ENST00000558014.5:c.-54-56206G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47703539-G-A
• chr15-47703539-G-C
• chr15-47703539-G-T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-54-56206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,040 control chromosomes in the GnomAD database, including 2,725 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 0.18 (2725 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-54-56206G>A		intron_variant	Intron 4 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-54-56206G>A		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-54-56206G>A		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-54-56206G>A		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26720 AN: 151924 Hom.: 2721 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.176 AC: 26734 AN: 152040 Hom.: 2725 Cov.: 32 AF XY: 0.178 AC XY: 13197 AN XY: 74294

African (AFR) AF: 0.0669 AC: 2778 AN: 41496

American (AMR) AF: 0.192 AC: 2934 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3468

East Asian (EAS) AF: 0.138 AC: 716 AN: 5180

South Asian (SAS) AF: 0.234 AC: 1124 AN: 4806

European-Finnish (FIN) AF: 0.239 AC: 2512 AN: 10532

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15270 AN: 67976

Other (OTH) AF: 0.187 AC: 393 AN: 2106

Alfa AF: 0.193 Hom.: 2003

Bravo AF: 0.169

Asia WGS AF: 0.148 AC: 514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.073
DANN	Benign	0.64
PhyloP100		-1.4
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: rs11634811; hg19: chr15-47995736;