9-89379111-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001371194.2(SEMA4D):​c.2182C>T​(p.Leu728Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,614,178 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00067 ( 11 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

8
10

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.53
Variant links:
Genes affected
SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is 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 -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.007683456).
BP6
Variant 9-89379111-G-A is Benign according to our data. Variant chr9-89379111-G-A is described in ClinVar as [Benign]. Clinvar id is 3044594.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00651 (991/152294) while in subpopulation AFR AF= 0.0224 (931/41558). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA4DNM_001371194.2 linkuse as main transcriptc.2182C>T p.Leu728Phe missense_variant 16/16 ENST00000422704.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA4DENST00000422704.7 linkuse as main transcriptc.2182C>T p.Leu728Phe missense_variant 16/161 NM_001371194.2 P1Q92854-1

Frequencies

GnomAD3 genomes
AF:
0.00652
AC:
992
AN:
152176
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0225
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00314
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00174
AC:
437
AN:
251364
Hom.:
1
AF XY:
0.00141
AC XY:
192
AN XY:
135872
show subpopulations
Gnomad AFR exome
AF:
0.0231
Gnomad AMR exome
AF:
0.00133
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00114
GnomAD4 exome
AF:
0.000672
AC:
982
AN:
1461884
Hom.:
11
Cov.:
31
AF XY:
0.000587
AC XY:
427
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0243
Gnomad4 AMR exome
AF:
0.00148
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.00126
GnomAD4 genome
AF:
0.00651
AC:
991
AN:
152294
Hom.:
11
Cov.:
32
AF XY:
0.00632
AC XY:
471
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.0224
Gnomad4 AMR
AF:
0.00314
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00426
Alfa
AF:
0.00114
Hom.:
3
Bravo
AF:
0.00784
ESP6500AA
AF:
0.0193
AC:
85
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.00207
AC:
251
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

SEMA4D-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesJan 29, 2020This 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
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.34
T;T;T;T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.74
.;.;T;.
MetaRNN
Benign
0.0077
T;T;T;T
MetaSVM
Benign
-0.32
T
MutationAssessor
Uncertain
2.4
M;M;M;M
MutationTaster
Benign
0.81
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.99
N;N;N;N
REVEL
Uncertain
0.37
Sift
Uncertain
0.0050
D;D;D;D
Sift4G
Uncertain
0.051
T;T;T;T
Polyphen
1.0
D;D;D;D
Vest4
0.35
MVP
0.51
MPC
0.90
ClinPred
0.017
T
GERP RS
4.5
Varity_R
0.063
gMVP
0.65

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: rs79522330; hg19: chr9-91994026; API