Genetic Variant SEMA4B:p.Arg184Ser (chr15-90221048-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198925.4(SEMA4B):c.550C>A(p.Arg184Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R184C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SEMA4B
NM_198925.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.55

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198925.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA4B	NM_198925.4	MANE Select	c.550C>A	p.Arg184Ser	missense	Exon 5 of 14	NP_945119.1	Q9NPR2-1
SEMA4B	NM_001324034.3		c.550C>A	p.Arg184Ser	missense	Exon 5 of 14	NP_001310963.1
SEMA4B	NM_001324031.4		c.550C>A	p.Arg184Ser	missense	Exon 6 of 15	NP_001310960.2	Q9NPR2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA4B	ENST00000411539.7	TSL:1 MANE Select	c.550C>A	p.Arg184Ser	missense	Exon 5 of 14	ENSP00000394720.2	Q9NPR2-1
SEMA4B	ENST00000332496.10	TSL:1	c.550C>A	p.Arg184Ser	missense	Exon 6 of 15	ENSP00000332204.6	Q9NPR2-1
SEMA4B	ENST00000558065.1	TSL:1	n.751C>A		non_coding_transcript_exon	Exon 2 of 11

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1458704

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725214

African (AFR)

AF:

0.00

AC:

AN:

33434

American (AMR)

AF:

0.00

AC:

AN:

44314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85312

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53286

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110660

Other (OTH)

AF:

0.00

AC:

AN:

60276

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.053

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.036

MetaRNN

Uncertain

0.61

MetaSVM

Benign

-0.89

PhyloP100

1.6

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Vest4

0.68

MVP

0.48

MPC

0.90

ClinPred

1.0

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.91

Mutation Taster

=55/45

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over