15-47696962-A-G

Position:

• chr15-47696962-A-G

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-54-62783A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 152,118 control chromosomes in the GnomAD database, including 8,457 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 0.30 (8457 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-54-62783A>G		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-54-62783A>G		intron_variant		1		ENSP00000452815	A1
SEMA6D	ENST00000559184.5	c.-54-62783A>G		intron_variant		4		ENSP00000453097
SEMA6D	ENST00000560636.5	c.-54-62783A>G		intron_variant		4		ENSP00000453420

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45317 AN: 152000 Hom.: 8454 Cov.: 32

Gnomad AFR AF: 0.0810

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.298 AC: 45317 AN: 152118 Hom.: 8457 Cov.: 32 AF XY: 0.294 AC XY: 21877 AN XY: 74366

Gnomad4 AFR AF: 0.0808

Gnomad4 AMR AF: 0.343

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.274

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.328

Alfa AF: 0.313 Hom.: 1640

Bravo AF: 0.292

Asia WGS AF: 0.243 AC: 844 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.47
DANN	Benign	0.81

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs955845; hg19: chr15-47989159;