9-89378700-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001371194.2(SEMA4D):​c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00634 in 1,608,650 control chromosomes in the GnomAD database, including 554 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 315 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 239 hom. )

Consequence

SEMA4D
NM_001371194.2 3_prime_UTR

Scores

2

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.596
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 (BayesDel_noAF=-0.79).
BP6
Variant 9-89378700-G-A is Benign according to our data. Variant chr9-89378700-G-A is described in ClinVar as [Benign]. Clinvar id is 3039346.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SEMA4DNM_001371194.2 linkuse as main transcriptc.*4C>T 3_prime_UTR_variant 16/16 ENST00000422704.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SEMA4DENST00000422704.7 linkuse as main transcriptc.*4C>T 3_prime_UTR_variant 16/161 NM_001371194.2 P1Q92854-1

Frequencies

GnomAD3 genomes
AF:
0.0332
AC:
5052
AN:
152178
Hom.:
313
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.115
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0127
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.000808
Gnomad OTH
AF:
0.0248
GnomAD3 exomes
AF:
0.00877
AC:
2198
AN:
250752
Hom.:
117
AF XY:
0.00622
AC XY:
843
AN XY:
135562
show subpopulations
Gnomad AFR exome
AF:
0.119
Gnomad AMR exome
AF:
0.00547
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000393
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000441
Gnomad OTH exome
AF:
0.00359
GnomAD4 exome
AF:
0.00352
AC:
5122
AN:
1456354
Hom.:
239
Cov.:
30
AF XY:
0.00307
AC XY:
2220
AN XY:
724286
show subpopulations
Gnomad4 AFR exome
AF:
0.117
Gnomad4 AMR exome
AF:
0.00636
Gnomad4 ASJ exome
AF:
0.0000768
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000302
Gnomad4 FIN exome
AF:
0.0000188
Gnomad4 NFE exome
AF:
0.000354
Gnomad4 OTH exome
AF:
0.00756
GnomAD4 genome
AF:
0.0333
AC:
5072
AN:
152296
Hom.:
315
Cov.:
33
AF XY:
0.0316
AC XY:
2351
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.115
Gnomad4 AMR
AF:
0.0127
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000794
Gnomad4 OTH
AF:
0.0246
Alfa
AF:
0.0153
Hom.:
61
Bravo
AF:
0.0375
Asia WGS
AF:
0.00953
AC:
33
AN:
3478
EpiCase
AF:
0.000545
EpiControl
AF:
0.000652

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 SciencesNov 26, 2019This 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
-0.79
CADD
Benign
1.1
DANN
Benign
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs73654771; hg19: chr9-91993615; API