rs4775692

Positions:

• chr15-47519858-C-A

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-87+49313C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,220 control chromosomes in the GnomAD database, including 940 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 0.092 (940 hom., cov: 33)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

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=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-87+49313C>A		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-87+49313C>A		intron_variant		1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-87+49313C>A		intron_variant		4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-171+49313C>A		intron_variant		4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.0922 AC: 14027 AN: 152100 Hom.: 939 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.0900

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0956

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

GnomAD4 genome AF: 0.0922 AC: 14040 AN: 152220 Hom.: 940 Cov.: 33 AF XY: 0.0942 AC XY: 7012 AN XY: 74420

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.0895

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0704 Hom.: 70

Bravo AF: 0.106

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	11
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4775692; hg19: chr15-47812055;