chr15-47753784-G-T

Variant names:

• chr15-47753784-G-T
• rs7167021
• NM_001358351.3:c.-54-5961G>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.-54-5961G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 152,054 control chromosomes in the GnomAD database, including 3,842 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 0.21 (3842 hom., cov: 32)
• Consequence: SEMA6D NM_001358351.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221
• Publications: 1 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358351.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	NM_001358351.3	MANE Select	c.-54-5961G>T		intron	N/A	NP_001345280.1
	SEMA6D	NM_001358352.2		c.-54-5961G>T		intron	N/A	NP_001345281.1
	SEMA6D	NM_153618.2		c.-54-5961G>T		intron	N/A	NP_705871.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA6D	ENST00000536845.7	TSL:2 MANE Select	c.-54-5961G>T		intron	N/A	ENSP00000446152.3
	SEMA6D	ENST00000316364.9	TSL:1	c.-54-5961G>T		intron	N/A	ENSP00000324857.5
	SEMA6D	ENST00000354744.8	TSL:1	c.-54-5961G>T		intron	N/A	ENSP00000346786.4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32146 AN: 151936 Hom.: 3844 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.00598

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.211 AC: 32147 AN: 152054 Hom.: 3842 Cov.: 32 AF XY: 0.211 AC XY: 15701 AN XY: 74308

African (AFR) AF: 0.144 AC: 5995 AN: 41490

American (AMR) AF: 0.191 AC: 2916 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3470

East Asian (EAS) AF: 0.00600 AC: 31 AN: 5168

South Asian (SAS) AF: 0.191 AC: 918 AN: 4816

European-Finnish (FIN) AF: 0.282 AC: 2979 AN: 10556

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17659 AN: 67948

Other (OTH) AF: 0.217 AC: 458 AN: 2114

Alfa AF: 0.246 Hom.: 886

Bravo AF: 0.196

Asia WGS AF: 0.108 AC: 377 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.72
PhyloP100		0.22
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: rs7167021; hg19: chr15-48045981;