15-47570766-G-A

Position:

• chr15-47570766-G-A

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-86-30099G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,120 control chromosomes in the GnomAD database, including 2,210 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 0.13 (2210 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.78

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=-0.26).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-86-30099G>A		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-86-30099G>A		intron_variant		1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-86-30099G>A		intron_variant		4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-170-30099G>A		intron_variant		4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19430 AN: 152002 Hom.: 2204 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.0832

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.0129

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0368

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0623

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.128 AC: 19459 AN: 152120 Hom.: 2210 Cov.: 32 AF XY: 0.123 AC XY: 9175 AN XY: 74374

Gnomad4 AFR AF: 0.304

Gnomad4 AMR AF: 0.0830

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0717

Gnomad4 FIN AF: 0.0368

Gnomad4 NFE AF: 0.0623

Gnomad4 OTH AF: 0.114

Alfa AF: 0.0878 Hom.: 222

Bravo AF: 0.141

Asia WGS AF: 0.0620 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	15
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9806310; hg19: chr15-47862963;