rs8034190

Positions:

• chr15-47389170-G-A
• chr15-47389170-G-T

Variant summary

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

The ENST00000558014.5(SEMA6D):​c.-238-23223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 151,922 control chromosomes in the GnomAD database, including 3,913 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 0.22 (3913 hom., cov: 32)
• Consequence: SEMA6D ENST00000558014.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001198999.2	c.-238-23223G>A		intron_variant			NP_001185928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000559799.5	n.510+6391C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.219 AC: 33237 AN: 151804 Hom.: 3911 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.0407

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.235

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

GnomAD4 genome AF: 0.219 AC: 33260 AN: 151922 Hom.: 3913 Cov.: 32 AF XY: 0.215 AC XY: 15944 AN XY: 74250

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.0408

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.232

Alfa AF: 0.0625 Hom.: 76

Bravo AF: 0.223

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8034190; hg19: chr15-47681367;