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GeneBe

15-90221017-G-C

Variant summary

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

The NM_198925.4(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
NM_198925.4 missense

Scores

17

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]

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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA4BNM_198925.4 linkuse as main transcriptc.519G>C p.Lys173Asn missense_variant 5/14 ENST00000411539.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA4BENST00000411539.7 linkuse as main transcriptc.519G>C p.Lys173Asn missense_variant 5/141 NM_198925.4 P1Q9NPR2-1

Frequencies

GnomAD3 genomes
AF:
0.00413
AC:
629
AN:
152228
Hom.:
2
Cov.:
33
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.:
1
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.:
18
Cov.:
33
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.:
2
Cov.:
33
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.:
2
Bravo
AF:
0.00342
TwinsUK
AF:
0.00324
AC:
12
ALSPAC
AF:
0.00415
AC:
16
ESP6500AA
AF:
0.000242
AC:
1
ESP6500EA
AF:
0.00571
AC:
48
ExAC
AF:
0.00358
AC:
433
Asia WGS
AF:
0.000577
AC:
2
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 submitterclinical testingCeGaT Center for Human Genetics TuebingenNov 01, 2022SEMA4B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.70
T
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
N
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.0053
T;T
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.28
T
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
T
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.

Other links and lift over

dbSNP: rs150569383; hg19: chr15-90764249; COSMIC: COSV60172872; COSMIC: COSV60172872; API