Variant rs17559084 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001384900.1(SEMA3D):c.1578G>A(p.Leu526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,609,492 control chromosomes in the GnomAD database, including 76,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4880 hom., cov: 32)

Exomes 𝑓: 0.30 ( 71253 hom. )

Consequence

SEMA3D
NM_001384900.1 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.516

Variant links:

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

SEMA3D links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.5).

BP6

Variant 7-85015184-C-T is Benign according to our data. Variant chr7-85015184-C-T is described in ClinVar as [Benign]. Clinvar id is 3060649.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.516 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3D	NM_001384900.1 linkuse as main transcript	c.1578G>A	p.Leu526=	synonymous_variant	16/19	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11 linkuse as main transcript	c.1578G>A	p.Leu526=	synonymous_variant	16/19	5	NM_001384900.1	ENSP00000284136	P1
SEMA3D	ENST00000484038.1 linkuse as main transcript	n.704G>A		non_coding_transcript_exon_variant	7/10	1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

34977

AN:

151626

Hom.:

4883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0857

Gnomad AMI

AF:

0.356

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.0632

Gnomad SAS

AF:

0.187

Gnomad FIN

AF:

0.230

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.242

AC:

60343

AN:

249844

Hom.:

8633

AF XY:

0.250

AC XY:

33821

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.287

Gnomad EAS exome

AF:

0.0625

Gnomad SAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.330

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.303

AC:

441624

AN:

1457750

Hom.:

71253

Cov.:

AF XY:

0.301

AC XY:

218397

AN XY:

725132

show subpopulations

Gnomad4 AFR exome

AF:

0.0764

Gnomad4 AMR exome

AF:

0.156

Gnomad4 ASJ exome

AF:

0.294

Gnomad4 EAS exome

AF:

0.0540

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.338

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.230

AC:

34968

AN:

151742

Hom.:

4880

Cov.:

AF XY:

0.225

AC XY:

16704

AN XY:

74140

show subpopulations

Gnomad4 AFR

AF:

0.0854

Gnomad4 AMR

AF:

0.221

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.0632

Gnomad4 SAS

AF:

0.187

Gnomad4 FIN

AF:

0.230

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.253

Alfa

AF:

0.307

Hom.:

12277

Bravo

AF:

0.221

Asia WGS

AF:

0.118

AC:

413

AN:

3478

EpiCase

AF:

0.335

EpiControl

AF:

0.329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3D-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

9.0

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over