rs17374298

chr15-47502281-G-Cchr15-47502281-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000558014.5(SEMA6D):c.-87+31736G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,146 control chromosomes in the GnomAD database, including 2,543 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 0.16 (2543 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001198999.2	c.-87+31736G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-87+31736G>C		intron_variant		1		A1
SEMA6D	ENST00000559184.5	c.-87+31736G>C		intron_variant		4
SEMA6D	ENST00000560636.5	c.-171+31736G>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24350 AN: 152028 Hom.: 2548 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.0473

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.220

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.160 AC: 24336 AN: 152146 Hom.: 2543 Cov.: 32 AF XY: 0.165 AC XY: 12256 AN XY: 74366

Gnomad4 AFR AF: 0.0394

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.0474

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.220

Gnomad4 OTH AF: 0.165

Alfa AF: 0.180 Hom.: 389

Bravo AF: 0.140

Asia WGS AF: 0.129 AC: 450 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	20
Dann	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17374298; hg19: chr15-47794478;