Variant 15-90221017-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000411539.7(SEMA4B):c.519G>C(p.Lys173Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,610,804 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0041 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0038 ( 18 hom. )

Consequence

SEMA4B
ENST00000411539.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.49

Variant links:

Genes affected

SEMA4B (HGNC:10730): (semaphorin 4B) Predicted to enable chemorepellent activity and semaphorin receptor binding activity. Predicted to be involved in several processes, including generation of neurons; neural crest cell migration; and semaphorin-plexin signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in extracellular space. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4B 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 (MetaRNN=0.005307883).

BP6

Variant 15-90221017-G-C is Benign according to our data. Variant chr15-90221017-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2645704.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4B	NM_198925.4 linkuse as main transcript	c.519G>C	p.Lys173Asn	missense_variant	5/14	ENST00000411539.7	NP_945119.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4B	ENST00000411539.7 linkuse as main transcript	c.519G>C	p.Lys173Asn	missense_variant	5/14	1	NM_198925.4	ENSP00000394720	P1	Q9NPR2-1

Frequencies

GnomAD3 genomes

AF:

0.00413

AC:

629

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.0230

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00527

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00323

AC:

787

AN:

243692

Hom.:

AF XY:

0.00321

AC XY:

424

AN XY:

131970

show subpopulations

Gnomad AFR exome

AF:

0.000403

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00282

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00442

Gnomad NFE exome

AF:

0.00510

Gnomad OTH exome

AF:

0.00489

GnomAD4 exome

AF:

0.00376

AC:

5482

AN:

1458458

Hom.:

Cov.:

AF XY:

0.00385

AC XY:

2792

AN XY:

725110

show subpopulations

Gnomad4 AFR exome

AF:

0.000748

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00257

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00562

Gnomad4 NFE exome

AF:

0.00429

Gnomad4 OTH exome

AF:

0.00353

GnomAD4 genome

AF:

0.00413

AC:

629

AN:

152346

Hom.:

Cov.:

AF XY:

0.00401

AC XY:

299

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00359

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00527

Gnomad4 NFE

AF:

0.00666

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00548

Hom.:

Bravo

AF:

0.00342

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000242

AC:

ESP6500EA

AF:

0.00571

AC:

ExAC

AF:

0.00358

AC:

433

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

SEMA4B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.032

DANN

Benign

0.61

DEOGEN2

Benign

0.013

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.71

.;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.0053

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.43

N;N

REVEL

Benign

0.019

Sift

Benign

0.45

T;T

Sift4G

Benign

0.42

T;T

Vest4

0.15

MVP

0.030

MPC

0.31

ClinPred

0.0034

GERP RS

-11

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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