rs1224660

Positions:

• chr15-47708565-T-C

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-54-51180T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 152,282 control chromosomes in the GnomAD database, including 63,529 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 0.91 (63529 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.945 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA6D	NM_001198999.2	c.-54-51180T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-54-51180T>C		intron_variant		1		A1
SEMA6D	ENST00000559184.5	c.-54-51180T>C		intron_variant		4
SEMA6D	ENST00000560636.5	c.-54-51180T>C		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.909 AC: 138346 AN: 152164 Hom.: 63490 Cov.: 32

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.861

Gnomad ASJ AF: 0.962

Gnomad EAS AF: 0.494

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.951

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.909 AC: 138445 AN: 152282 Hom.: 63529 Cov.: 32 AF XY: 0.904 AC XY: 67326 AN XY: 74456

Gnomad4 AFR AF: 0.906

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.962

Gnomad4 EAS AF: 0.495

Gnomad4 SAS AF: 0.839

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.951

Gnomad4 OTH AF: 0.904

Alfa AF: 0.935 Hom.: 33165

Bravo AF: 0.899

Asia WGS AF: 0.672 AC: 2337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1224660; hg19: chr15-48000762;