chr15-47622815-T-C

Position:

• chr15-47622815-T-C

Variant summary

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

The NM_001198999.2(SEMA6D):​c.-55+21919T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,100 control chromosomes in the GnomAD database, including 3,883 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 0.20 (3883 hom., cov: 32)
• Consequence: SEMA6D NM_001198999.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-55+21919T>C		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000558014.5	c.-55+21919T>C		intron_variant		1		ENSP00000452815.1
SEMA6D	ENST00000559184.5	c.-55+21919T>C		intron_variant		4		ENSP00000453097.1
SEMA6D	ENST00000560636.5	c.-55+19357T>C		intron_variant		4		ENSP00000453420.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30890 AN: 151982 Hom.: 3882 Cov.: 32

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.311

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.203 AC: 30892 AN: 152100 Hom.: 3883 Cov.: 32 AF XY: 0.206 AC XY: 15342 AN XY: 74350

Gnomad4 AFR AF: 0.0644

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.311

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.200

Alfa AF: 0.259 Hom.: 716

Bravo AF: 0.185

Asia WGS AF: 0.238 AC: 827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
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: rs1435752; hg19: chr15-47915012;