chr15-47288742-T-C

Variant names:

• chr15-47288742-T-C
• rs766132
• ENST00000558014.5:c.-239+104324T>C

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-239+104324T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 152,006 control chromosomes in the GnomAD database, including 23,318 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 0.55 (23318 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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 (NFE) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-239+104324T>C		intron_variant	Intron 1 of 19		NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-239+104324T>C		intron_variant	Intron 1 of 19	1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-239+47372T>C		intron_variant	Intron 2 of 5	4		ENSP00000453097.1

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83391 AN: 151888 Hom.: 23299 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.695

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.564

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.549 AC: 83464 AN: 152006 Hom.: 23318 Cov.: 32 AF XY: 0.548 AC XY: 40718 AN XY: 74298

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.586

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.564

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.544

Alfa AF: 0.575 Hom.: 49034

Bravo AF: 0.544

Asia WGS AF: 0.407 AC: 1414 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	0.57
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs766132; hg19: chr15-47580939;