15-47586424-G-T

Position:

• chr15-47586424-G-T

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-86-14441G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,996 control chromosomes in the GnomAD database, including 5,748 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 0.26 (5748 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-14441G>T		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-86-14441G>T		intron_variant		1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-14441G>T		intron_variant		4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-14441G>T		intron_variant		4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39202 AN: 151874 Hom.: 5738 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.258 AC: 39221 AN: 151996 Hom.: 5748 Cov.: 32 AF XY: 0.257 AC XY: 19074 AN XY: 74306

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.363

Gnomad4 ASJ AF: 0.338

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.301

Alfa AF: 0.269 Hom.: 3183

Bravo AF: 0.267

Asia WGS AF: 0.284 AC: 986 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1865648; hg19: chr15-47878621;