rs11634811

Positions:

• chr15-47703539-G-A
• chr15-47703539-G-C
• chr15-47703539-G-T

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-54-56206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,040 control chromosomes in the GnomAD database, including 2,725 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 0.18 (2725 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-54-56206G>A		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-54-56206G>A		intron_variant		1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-54-56206G>A		intron_variant		4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-54-56206G>A		intron_variant		4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26720 AN: 151924 Hom.: 2721 Cov.: 32

Gnomad AFR AF: 0.0670

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.176 AC: 26734 AN: 152040 Hom.: 2725 Cov.: 32 AF XY: 0.178 AC XY: 13197 AN XY: 74294

Gnomad4 AFR AF: 0.0669

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.234

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.187

Alfa AF: 0.176 Hom.: 848

Bravo AF: 0.169

Asia WGS AF: 0.148 AC: 514 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.073
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: rs11634811; hg19: chr15-47995736;