rs765

Variant names:

• chr15-47743488-G-A
• rs765
• NM_001358351.3:c.-54-16257G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47743488-G-A
• chr15-47743488-G-T

Variant summary

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

The NM_001358351.3(SEMA6D):​c.-54-16257G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 151,958 control chromosomes in the GnomAD database, including 17,868 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 0.47 (17868 hom., cov: 32)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.191
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001358351.3	c.-54-16257G>A		intron_variant	Intron 1 of 18	ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7	c.-54-16257G>A		intron_variant	Intron 1 of 18	2	NM_001358351.3	ENSP00000446152.3

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72109 AN: 151840 Hom.: 17864 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.475 AC: 72134 AN: 151958 Hom.: 17868 Cov.: 32 AF XY: 0.478 AC XY: 35537 AN XY: 74272

African (AFR) AF: 0.385 AC: 15952 AN: 41422

American (AMR) AF: 0.445 AC: 6797 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 1919 AN: 3466

East Asian (EAS) AF: 0.183 AC: 946 AN: 5170

South Asian (SAS) AF: 0.533 AC: 2564 AN: 4808

European-Finnish (FIN) AF: 0.579 AC: 6109 AN: 10544

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.534 AC: 36317 AN: 67962

Other (OTH) AF: 0.476 AC: 1005 AN: 2112

Alfa AF: 0.505 Hom.: 66157

Bravo AF: 0.453

Asia WGS AF: 0.374 AC: 1300 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.48
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765; hg19: chr15-48035685;