Variant rs16960071 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000358066.8(SEMA6D):c.1647-5T>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,600,272 control chromosomes in the GnomAD database, including 1,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.024 ( 88 hom., cov: 32)

Exomes 𝑓: 0.032 ( 1022 hom. )

Consequence

SEMA6D
ENST00000358066.8 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.009559

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.91

Variant links:

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]

SEMA6D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA6D	NM_001358351.3 linkuse as main transcript	c.1647-44T>A		intron_variant		ENST00000536845.7	NP_001345280.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA6D	ENST00000536845.7 linkuse as main transcript	c.1647-44T>A		intron_variant		2	NM_001358351.3	ENSP00000446152	P4	Q8NFY4-1

Frequencies

GnomAD3 genomes

AF:

0.0238

AC:

3618

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00529

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.0577

Gnomad SAS

AF:

0.0805

Gnomad FIN

AF:

0.0422

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0293

Gnomad OTH

AF:

0.0181

GnomAD3 exomes

AF:

0.0332

AC:

8304

AN:

250224

Hom.:

270

AF XY:

0.0354

AC XY:

4788

AN XY:

135274

show subpopulations

Gnomad AFR exome

AF:

0.00550

Gnomad AMR exome

AF:

0.00981

Gnomad ASJ exome

AF:

0.00518

Gnomad EAS exome

AF:

0.0682

Gnomad SAS exome

AF:

0.0747

Gnomad FIN exome

AF:

0.0460

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0251

GnomAD4 exome

AF:

0.0324

AC:

46866

AN:

1448066

Hom.:

1022

Cov.:

AF XY:

0.0335

AC XY:

24175

AN XY:

721374

show subpopulations

Gnomad4 AFR exome

AF:

0.00419

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00478

Gnomad4 EAS exome

AF:

0.0430

Gnomad4 SAS exome

AF:

0.0683

Gnomad4 FIN exome

AF:

0.0449

Gnomad4 NFE exome

AF:

0.0311

Gnomad4 OTH exome

AF:

0.0319

GnomAD4 genome

AF:

0.0237

AC:

3613

AN:

152206

Hom.:

Cov.:

AF XY:

0.0259

AC XY:

1927

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00527

Gnomad4 AMR

AF:

0.0111

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.0578

Gnomad4 SAS

AF:

0.0795

Gnomad4 FIN

AF:

0.0422

Gnomad4 NFE

AF:

0.0293

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0173

Hom.:

Bravo

AF:

0.0197

Asia WGS

AF:

0.0790

AC:

274

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0096

dbscSNV1_RF

Benign

0.024

SpliceAI score (max)

0.51

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.51

Position offset: 2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over