9-89379111-G-A
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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
NM_001371194.2 missense
Scores
8
10
Clinical Significance
Conservation
PhyloP100: 1.53
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]
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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 |
---|---|---|---|---|---|---|---|
SEMA4D | NM_001371194.2 | c.2182C>T | p.Leu728Phe | missense_variant | 16/16 | ENST00000422704.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SEMA4D | ENST00000422704.7 | c.2182C>T | p.Leu728Phe | missense_variant | 16/16 | 1 | NM_001371194.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00652 AC: 992AN: 152176Hom.: 11 Cov.: 32
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GnomAD3 exomes AF: 0.00174 AC: 437AN: 251364Hom.: 1 AF XY: 0.00141 AC XY: 192AN XY: 135872
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GnomAD4 exome AF: 0.000672 AC: 982AN: 1461884Hom.: 11 Cov.: 31 AF XY: 0.000587 AC XY: 427AN XY: 727246
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GnomAD4 genome AF: 0.00651 AC: 991AN: 152294Hom.: 11 Cov.: 32 AF XY: 0.00632 AC XY: 471AN XY: 74472
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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 provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 29, 2020 | 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
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
.;.;T;.
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
T;T;T;T
Polyphen
D;D;D;D
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at