rs11857760

Variant names:

• chr15-47698643-A-G
• rs11857760
• ENST00000558014.5:c.-54-61102A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-47698643-A-G
• chr15-47698643-A-T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-54-61102A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.584 in 152,018 control chromosomes in the GnomAD database, including 26,472 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 0.58 (26472 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-54-61102A>G		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.-54-61102A>G		intron_variant	Intron 4 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-54-61102A>G		intron_variant	Intron 5 of 5	4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-54-61102A>G		intron_variant	Intron 5 of 5	4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88721 AN: 151900 Hom.: 26448 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.652

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.512

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.584 AC: 88790 AN: 152018 Hom.: 26472 Cov.: 32 AF XY: 0.580 AC XY: 43067 AN XY: 74270

African (AFR) AF: 0.483 AC: 20051 AN: 41498

American (AMR) AF: 0.593 AC: 9049 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.652 AC: 2265 AN: 3472

East Asian (EAS) AF: 0.382 AC: 1972 AN: 5168

South Asian (SAS) AF: 0.513 AC: 2474 AN: 4818

European-Finnish (FIN) AF: 0.630 AC: 6635 AN: 10540

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.651 AC: 44240 AN: 67956

Other (OTH) AF: 0.607 AC: 1281 AN: 2112

Alfa AF: 0.634 Hom.: 138505

Bravo AF: 0.580

Asia WGS AF: 0.444 AC: 1540 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.059
DANN	Benign	0.55
PhyloP100		-2.0
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: rs11857760; hg19: chr15-47990840;