rs12593270

Positions:

• chr15-47455143-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000558014.5(SEMA6D):​c.-158-15331G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,350 control chromosomes in the GnomAD database, including 3,876 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 0.22 (3876 hom., cov: 31)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222

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]

ACMG classification

Verdict is Benign. Variant got -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 = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001198999.2	c.-158-15331G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-158-15331G>C		intron_variant		1		A1
SEMA6D	ENST00000559184.5	c.-158-15331G>C		intron_variant		4
SEMA6D	ENST00000560636.5	c.-242-15331G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33918 AN: 151242 Hom.: 3876 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.224 AC: 33932 AN: 151350 Hom.: 3876 Cov.: 31 AF XY: 0.229 AC XY: 16933 AN XY: 73906

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.364

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.213

Alfa AF: 0.221 Hom.: 504

Bravo AF: 0.214

Asia WGS AF: 0.259 AC: 903 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	3.6
DANN	Benign	0.52

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12593270; hg19: chr15-47747340;