rs1898111

Variant names:

• chr15-47600101-G-A
• rs1898111
• ENST00000558014.5:c.-86-764G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-47600101-G-A
• chr15-47600101-G-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.-86-764G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 151,888 control chromosomes in the GnomAD database, including 39,754 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 0.70 (39754 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 8 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.819 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.-86-764G>A		intron	N/A	NP_001185928.1	Q8NFY4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000558014.5	TSL:1	c.-86-764G>A		intron	N/A	ENSP00000452815.1	Q8NFY4-2
	SEMA6D	ENST00000559184.5	TSL:4	c.-86-764G>A		intron	N/A	ENSP00000453097.1	H0YL82
	SEMA6D	ENST00000560636.5	TSL:4	c.-170-764G>A		intron	N/A	ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106460 AN: 151772 Hom.: 39737 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.726

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.839

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.749

Gnomad FIN AF: 0.818

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.825

Gnomad OTH AF: 0.733

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

GnomAD4 genome AF: 0.701 AC: 106509 AN: 151888 Hom.: 39754 Cov.: 32 AF XY: 0.703 AC XY: 52212 AN XY: 74254

African (AFR) AF: 0.430 AC: 17786 AN: 41388

American (AMR) AF: 0.736 AC: 11217 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.839 AC: 2912 AN: 3470

East Asian (EAS) AF: 0.746 AC: 3841 AN: 5152

South Asian (SAS) AF: 0.750 AC: 3611 AN: 4814

European-Finnish (FIN) AF: 0.818 AC: 8650 AN: 10570

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.825 AC: 56050 AN: 67940

Other (OTH) AF: 0.730 AC: 1535 AN: 2102

Alfa AF: 0.789 Hom.: 87516

Bravo AF: 0.682

Asia WGS AF: 0.680 AC: 2366 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.50
PhyloP100		1.2
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: rs1898111; hg19: chr15-47892298;